CN107198685A - A kind of pharmaceutical composition for treating clear-cell carcinoma and application - Google Patents
A kind of pharmaceutical composition for treating clear-cell carcinoma and application Download PDFInfo
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- CN107198685A CN107198685A CN201710448010.5A CN201710448010A CN107198685A CN 107198685 A CN107198685 A CN 107198685A CN 201710448010 A CN201710448010 A CN 201710448010A CN 107198685 A CN107198685 A CN 107198685A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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Abstract
The present invention relates to a kind of pharmaceutical composition for treating clear-cell carcinoma and application.Present invention firstly discloses application of the composition in treatment clear-cell carcinoma medicine of wogonin and Sutent collectively as effective component.Experimental result confirms that abnormal rapid DNA is replicated and cell propagation is one of key character of tumour, and suppressing DNA replication dna can induce apoptosis of tumor cells.Wogonin is with Sutent composition compared with above two medicine is used alone, and the activity for suppressing renal cell carcinoma cell DNA replication dna and propagation and induction Apoptosis is higher, and the two has the effect for synergy of mutually promoting.Study and find simultaneously, wogonin is used in conjunction with Sutent composition, can effectively overcome renal cell carcinoma cell to the drug resistance of Sutent.With application prospect of the Sutent composition in renal cell carcinoma treatment extensively, the also treatment for clear-cell carcinoma provides more medicament selections to wogonin.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition for treating clear-cell carcinoma and application, belong to technical field of drug development.
Background technology
With the change of people life style and living environment, the morbidity and mortality of cancer are in rising trend,
As after coronary heart disease, the high illness of mankind's fatal rate second is also global focus health problem.Kidney is urinary system
Unite one of most common malignant tumour, the incidence of disease accounts for the 3% of all malignant tumours, and its incidence of disease becomes in rising in recent years
Gesture.Shown according to Cancer center of world data, the U.S. in 2015 predicts that new patients with renal cell carcinoma number is 61,560, tumour-specific
Died Patients number is also up to 14,080, occupies death rate prostatitis.The number of patients of China's kidney also increases year by year, kidney is new
Hair and death are respectively 668000 and 234000, and the 15th and 17 of morbidity and mortality is occupied respectively, into
For uropoiesis male genital second tumour.
Clear-cell carcinoma (renal cell carcinoma, RCC) is originating from the substantive renal cells of kidney, the incidence of disease
Height, about 90% renal cancer is RCC.RCC is for traditional radiotherapy, chemotherapy and insensitive.With treatment level raising and
The innovation of clinical medicine, especially as the development of molecular genetics, increasing signaling pathway molecule is found in row in RCC
Make important function.On this basis, various countries have approved many EGFR-TKs of increasing targeted drug such as targeted inhibition
Inhibitor medicaments such as Sutent etc. be used to treat advanced metastatic RCC.The diagnosis and treatment of kidney achieve certain curative effect in recent years
Used with these molecular targeted therapies inseparable.Because patient benefits extremely limited by immunization therapy, therefore right
In RCC especially middle and advanced stage metastatic RCC, targeted drug treatment has turned into the therapeutic strategy that major guides are recommended, also as evening
The first-line treatment means of phase kidney.However, because tumour is a kind of height heterogeneity disease, with answering for molecular targeted agents
With the drug resistance problems of targeted drug are gradually exposed, and such as receive the patient of Sutent treatment although curative effect shows in the early stage
Write, but produced resistance in 5~10 months mostly, few patient's complete incidence graphs, this has had a strong impact on the curative effect of RCC treatments,
Add the difficulty of clinical treatment clear-cell carcinoma.In addition, targeted drug there is also certain side effect and expensive grade not
Foot, these all turn into the bottleneck of targeted therapy.So increase targeted drug sensitiveness, reduces dosage, overcomes drug resistance, open
Sending out new treatment turns into the primary study direction that kidney is treated.
Chinese medicine shows certain effect in the treatment of malignant tumour, and toxic side effect is smaller.Passed from effective antitumor
Isolated active natural compounds have the integrally-regulated feature of Mutiple Targets in system Chinese medicine, make it have potential improvement or reverse
Resistance advantage, is also one of important means of anti-cancer agent research and development.Labiatae (Labiatase) plant radix scutellariae be China simply
Conventional Chinese medicine.Wogonin is radix scutellariae and belongs to the flavone compound extracted in corresponding plant roots together, be radix scutellariae medicine effectively into
/ mono-.Research have shown wogonin there is anti-inflammatory, anti-oxidant, many bioactivity such as antiviral.
In addition, wogonin can be by increasing the content of reactive oxygen species in stomach cancer, induced tumor cell withers
Die, suppress the various ways such as resistance of new vessels generation and reverse chemotherapeutics around tumour and play antineoplastic function.
Nevertheless, about wogonin in terms of the application in preparing treatment clear-cell carcinoma medicine and molecular mechanism, the especially Chinese
Baicalein is increasing clear-cell carcinoma targeted drug sensitiveness, the problems such as reversing the effect in clear-cell carcinoma targeted drug resistance, still
Without research.
The content of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of pharmaceutical composition for treating clear-cell carcinoma and application.
Technical scheme is as follows：
The application of Sutent and wogonin composition in treatment clear-cell carcinoma medicine is prepared.
A kind of pharmaceutical composition for treating clear-cell carcinoma, including：Sutent and wogonin.
Wogonin can effectively suppress renal cell carcinoma cell propagation with Sutent drug regimen, and inducing DNA replicates obstacle,
Induce renal cell carcinoma cell apoptosis.
According to currently preferred, the mol ratio of the Sutent and wogonin is 1: (1~10).
According to currently preferred, the mol ratio of the Sutent and wogonin is 1:(1~8).
According to currently preferred, the mol ratio of the Sutent and wogonin is 1:(4~8).
According to currently preferred, the quality of the Sutent and wogonin account for described pharmaceutical composition 1~
99.5%.
Aforementioned pharmaceutical compositions, in addition to pharmaceutically acceptable excipient.
According to some embodiments of the present invention, in described pharmaceutical composition, the mol ratio of Chinese Sutent and baicalein
For 1:1~10, such as 1:1~9,1:1~8,1:1~7,1:1~6,1:1~5,1:1~4,1:1~3,1:1~2,1:2~
10、1:2~9,1:2~8,1:2~7,1:2~6,1:2~5,1:2~4,1:2~3,1:3~10,1:3~9,1:3~8,1:3
~7,1:3~6,1:3~5,1:3~4,1: 4~10,1:4~9,1:4~8,1:4~7,1:4~6,1:4~5,1:5~10,1
: 5~9,1: 5~8,1: 5~7,1:5~6,1:6~10,1:6~9,1:6~8,1:6~7,1:7~10,1:7~9,1:7~
8、1:8~10,1: 8~9 and 1:9~10；It is preferred that 1:6~10, more preferably 1:8~10.
According to an aspect of the present invention, the invention provides a kind of medicine box, the medicine box comprising the wogonin and
Sutent.
According to currently preferred, the mol ratio of the Sutent and wogonin is 1:(1~10).
According to currently preferred, the mol ratio of the Sutent and wogonin is 1:(1~8).
According to currently preferred, the mol ratio of the Sutent and wogonin is 1:(4~8).
According to currently preferred, the quality of the Sutent and wogonin account for described pharmaceutical composition 1~
99.5%.
According to some embodiments of the present invention, the quality of described Sutent and wogonin accounts for the drug regimen
The 1~99.5% of thing or medicine box quality, such as 1~99%, 1~90%, 1~80%, 1~70%, 1~60%, 1~50%, 1
~40%, 1~30%, 1~20%, 1~10%, 10~99.5%, 10~99%, 10~90%, 10~80%, 10~
70%th, 10~60%, 10~50%, 10~40%, 10~30%, 10~20%, 20~99.5%, 20~99%, 20~
90%th, 20~80%, 20~70%, 20~60%, 20~50%, 20~40%, 20~30%, 30~99.5%, 30~
99%th, 30~90%, 30~80%, 30~70%, 30~60%, 30~50%, 30~40%, 40~99.5%, 40~
99%th, 40~90%, 40~80%, 40~70%, 40~60%, 40~50%, 50~99.5%, 50~99%, 50~
90%th, 50~80%, 50~70%, 50~60%, 60~99.5%, 60~99%, 60~90%, 60~80%, 60~
70%th, 70~99.5%, 70~99%, 70~90%, 70~80%, 80~99.5%, 80~99%, 80~90%, 90~
99.5% or 90~99%.
According to some embodiments of the application, described Sutent and the quality of wogonin account for the drug regimen
Thing or medicine box quality 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%,
15%th, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%,
30%th, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%,
45%th, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%,
60%th, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%,
75%th, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,
90%th, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5%.
Unless otherwise defined, all technical terms or proprietary vocabulary used herein have the common of technical field
The implication that technical staff is generally understood.
Wogonin (wogonin), also known as 5,7- dihydroxy -8- methoxyl group -2- phenyl -4H-1- benzofuran -4- ketone.
It is yellow needles thing under normal temperature, it is water insoluble, organic solvent is soluble in, such as ethanol, acetone.Wogonin is from Huang
The flavone compound extracted in the root of a kind of reed mentioned in ancient books, with the effect such as anti-inflammatory, reducing blood lipid, antithrombus formation.
Kidney is one of most common malignant tumour of urinary system, including clear-cell carcinoma, the nephroblastoma and carcinoma of renal pelvis etc..
Clear-cell carcinoma (renal cell carcinoma, RCC), also known as Grawitz's tumor, are the most common pathology classes of kidney
Type, accounts for the 80%~85% of kidney.RCC is initiated by the malignant tumour of the substantive renal cells of kidney.RCC is for tradition
Radiotherapy, chemotherapy and insensitive.
Targeted drug Sutent treatment clear-cell carcinoma is remarkably improved patient's progression free survival phase and Overall survival, is late
The standard fiest-tire medication of phase clear-cell carcinoma.But find that the medicine has higher adverse reaction rate in clinical practice, even
Some patientss affect the treatment or are discontinued because toxicity not can tolerate.In addition the medicine is easily occurred resistance to using patient after 5~10 months
The property of medicine, has a strong impact on therapeutic effect.
Treatment by Chinese herbs tumour, which has, improves the state of an illness, extension paracmasis, Small side effects, the late result spy such as good and low-cost
Point, has shown the advantage of uniqueness.
In clear-cell carcinoma research, analyzed commonly using HK cells's JEG-3 786-O and OS-RC-2 cell gene or
Influence of the medicine to renal cell carcinoma cell tumor characteristic.
Term " excipient " represents to refer to being commonly used for preparing particle and/or solid oral dosage form/and/or liquid injection
The pharmaceutically acceptable composition without any pharmacotoxicological effect of the pharmaceutical technology of dosage formulation.Excipient can play carrier, dilution
Agent or dissolving modifying agent, sorbefacient, stabilizer or the auxiliary agent of preparation and other effects.Preparing pharmaceutical composition
In useful excipient be typically it is safe and nontoxic and be medical science use and medicine use in it is acceptable.In this specification
Middle " excipient " used or " pharmaceutically acceptable excipient " include a kind of and a variety of such excipient.
Pharmaceutical composition and medicine box
Term " pharmaceutical composition " represents one or more compounds containing therapeutically effective amount and its pharmaceutically may be used
Dynamic isomer, solvate, hydrate or the salt of receiving, the mixture with other pharmaceutically acceptable carriers.Will be described
The purpose that compound is prepared into pharmaceutical composition is to be more easily administered to object.
Term " medicine box " or " kit " are used interchangeably in the application.This application discloses the institute comprising therapeutically effective amount
State therapeutic agent or the medicine box of pharmaceutical composition.According to some embodiments of the application, the medicine box is also comprising one or more
Other therapeutic agents.According to some embodiments of the application, the medicine box also includes operation instructions.According to certain of the application
A little embodiments, the medicine box also includes the device for corresponding administering mode, such as, but not limited to syringe needle.
Term " drug resistance " refers to biological or cell (specifically related to tumour cell and tumor patient herein) for medicine
The tolerance of thing effect.For example, after tumour cell is to drug resistant, the therapeutic action of medicine is just decreased obviously, need
Escalated dose just can guarantee that drug effect does not subtract.
Wogonin can be prepared into any one formulation pharmaceutically allowed, including but not limited to piece in the present invention
Agent, oral agents, electuary, injection, liposome, target administration injection pill, capsule, granule, pulvis, suppository, powder,
Paste, patch, parenteral solution, solution, suspension, spray, lotion, drops, liniment etc..Described pharmaceutical composition can be made into dry powder
Form, and with sterilized water or buffer solution mix that solution form is made before administration.The pH of the buffer solution is usually 3~
11, preferably 5~9, more preferably 7~8.
It is suitable that term " administration ", " giving " or " bestowing " refers to pass through the compound or pharmaceutical composition of doses
Administering mode gives object.
" administering mode " include but is not limited to oral administration, intravenous administration, administration in respiratory tract, sublingual administration,
Local administration, intramuscular adminstration, eye drops, Transdermal absorption, parenteral, Intraperitoneal medication, vagina administration, cheek are given
Any administering modes known in the art such as medicine, per rectum administration.Those skilled in the art should be recognized that the administering mode of object
Depending on Multiple factors, the factor includes position, the age of object, the order of severity of disease and the drug regimen of disease
Composition of thing etc..
In this application when " about " is used to modify numerical value, refer to the numerical value can fluctuate ± 10%, ± 9%,
± 8%, in the range of ± 7%, ± 6%, ± 5%, ± 4%, ± 3%, ± 2% or ± 1%.
Unless be otherwise noted in this application or otherwise clearly contradicted, in the context of description the application (including
In the context of claim) term " one kind " that uses, " one ", " described ", "the" and " at least one " and similar refer to
In generation, is interpreted covering odd number and plural number.Unless be otherwise noted in this application or otherwise clearly contradicted, institute in the application
The term "comprising" that uses, " having ", " comprising " and " containing " are interpreted open-ended term (" including but is not limited to ").Remove
Non- to be otherwise noted in this application or otherwise clearly contradicted, all methods described herein can be according to art technology
The understanding of personnel, is carried out in any suitable order.
All patents, patent application and the bibliography quoted in the application are incorporated by this Shen by reference
Please, its incorporated extent is individually recited as reference just as each document.If the application and provided herein is document between
In the presence of conflict, content that should be in the application is defined.
Beneficial effect
It is thin in treatment kidney collectively as the composition of effective component with Sutent present invention firstly discloses wogonin
Application in born of the same parents' cancer drug.Experimental result confirms, abnormal rapid DNA replicate and cell propagation be tumour key character it
One, suppressing DNA replication dna can induce apoptosis of tumor cells.Wogonin individually makes with Sutent composition with above two medicine
With compared to suppression renal cell carcinoma cell DNA replication dna and the activity of propagation and induction Apoptosis are higher, and the two is with mutually
Promote the effect of synergy.Study and find simultaneously, wogonin is used in conjunction with Sutent composition, effectively kidney can be overcome thin
Drug resistance of born of the same parents' cancer cell to Sutent.Wogonin and application of the Sutent composition in renal cell carcinoma treatment
Extensively, the also treatment for clear-cell carcinoma provides more medicament selections to prospect.
Brief description of the drawings
The column of Fig. 1, the wogonin of MTT experiment and Sutent composition to the growth inhibitory activity of clear-cell carcinoma
Figure；
Data in figure are the results of 3 parallel laboratory tests, and 5 repeating holes of experiment setting, are examined using T every time；* p is represented
≦0.05；* represents p≤0.01；
The wogonin and Sutent composition of Fig. 2, Tunel experiment induce the column of renal cell carcinoma cell apoptosis activity
Figure；
Data in figure are the results of 3 parallel laboratory tests, every time 5 random fields of experiment setting, and each visual field cell is total
Number is no less than 200, is examined using T；* represent to compare blank control group, p≤0.05；* represent compare blank control group, p≤
0.01；
The wogonin and Sutent composition of Fig. 3, EdU experiment suppress the post of renal cell carcinoma cell DNA replication dna efficiency
Shape figure；
Data in figure are the results of 3 parallel laboratory tests, every time 5 random fields of experiment setting, and each visual field cell is total
Number is no less than 200, is examined using T；* represent to compare blank control group, p≤0.05；* represent compare blank control group, p≤
0.01；
Fig. 4, the wogonin of MTT experiment and Sutent composition can effectively suppress Sutent drug resistance clear-cell carcinoma
The block diagram of the propagation of cell；
Data in figure are the results of 3 parallel laboratory tests, and 5 repeating holes of experiment setting, are examined using T every time；* phase is represented
Than blank control group, p≤0.05；* represents to compare blank control group, p≤0.01；
The wogonin and Sutent composition of Fig. 5, Tunel experiment can significantly induce Sutent drug resistance nephrocyte
The block diagram of cancer cell-apoptosis；
Data in figure are the results of 3 parallel laboratory tests, every time 5 random fields of experiment setting, and each visual field cell is total
Number is no less than 200, is examined using T；* represent to compare blank control group, p≤0.05；* represent compare blank control group, p≤
0.01；With
The wogonin and Sutent composition of Fig. 6, EdU experiment can effectively suppress Sutent drug resistance clear-cell carcinoma
The block diagram of the DNA replication dna efficiency of cell；
Data in figure are the results of 3 parallel laboratory tests, every time 5 random fields of experiment setting, and each visual field cell is total
Number is no less than 200, is examined using T；* represent to compare blank control group, p≤0.05；* represent compare blank control group, p≤
0.01。
Embodiment
Below in conjunction with the instantiation content that the present invention is furture elucidated, but protection scope of the present invention is not limited to this
A little examples.
Embodiment 1：Wogonin and Sutent composition are higher to the growth inhibitory activity of clear-cell carcinoma
This example demonstrates that wogonin and Sutent composition are higher to the growth inhibitory activity of clear-cell carcinoma.At this
In embodiment, the renal cell carcinoma cell is people's kidney clear cell adenocarcinoma cell 786-O and OS-RC-2 cell.
Experiment packet and administration final concentration are as follows：
Blank control group：The sub- wind (DMSO) of isometric excipient dimethyl
Wogonin low dose group：20 μm of ol/L wogonins
Wogonin high dose group：40 μm of ol/L wogonins
Sutent low dose group：5 μm of ol/L Sutents
Sutent high dose group：10 μm of ol/L Sutents
Composition A groups:+ 5 μm of ol/L Sutents of 10 μm of ol/L wogonins
Composition B groups：+ 5 μm of ol/L Sutents of 20 μm of ol/L wogonins
Composition C groups：+ 10 μm of ol/L Sutents of 20 μm of ol/L wogonins
Wogonin is purchased from Shanghai Yuan Ye bio tech ltd (production number ZCX-00023510-005), is dissolved in
0.1M (mol/L) mother liquor is configured in DMSO and in -20 DEG C of storages.Sutent has purchased from U.S.'s selleck biotechnologies
Limit company (production number S7781), is dissolved in being configured to 0.05M (mol/L) mother liquor in DMSO and in -20 DEG C of storages.MTT is thin
Born of the same parents breed and citotoxicity detection kit is purchased from green skies Bioisystech Co., Ltd (production number C0009).People's kidney is transparent thin
Born of the same parents adenocarcinoma cell 786-O (production number TCHu186) and OS-RC-2 (production number TCHu 40) cell are purchased from Chinese Academy of Sciences's allusion quotation
Type culture collection committee cell bank, cell culture uses RPMI-1640 culture mediums (Gibco companies of the U.S., production number
11875127) 10% (V/V) hyclone of addition (Gibco companies of the U.S., (production number 1099141), and add 100U/ml's
Penicillin and 100mg/ml streptomysins.All cells are with 37 DEG C, CO2Partial pressure is the CMC model of 5% (percentage by volume).
Tetrazolium bromide (MTT) is tested：By 786-O the and OS-RC-2 cells in exponential phase with 10 × 104/ ml cells
Concentration is inoculated with 96 porocyte culture plates, per the μ L of hole 100, if 5 multiple holes, is placed in 37 DEG C, 5%CO2Culture 24 hours in incubator
Left and right, then it is separately added into the RPMI-1640 complete mediums of the medicine containing each group.After being incubated 48 hours, 20 μ l 5mg/ are added per hole
Ml MTT working solutions.Culture plate is put back into 37 DEG C, 5%CO after shaking up2Continue in incubator after cultivating 4-6 hours, MTT will be contained
The supernatant of working solution is carefully removed, and 100 μ L dimethyl sulphoxide solutions are added per hole, culture plate is put into 37 DEG C, 5%CO2Culture
It is incubated in case, after purple crystal all dissolves and solution transparency is homogeneous (about 20 minutes), in multi-function microplate reader 570nm ripples
Strong point determines absorbance (OD), and cell survival rate is calculated with OD values.
Cell survival rate=(test group cell OD values-blank group cell OD values)/(cellular control unit OD values-blank group is thin
Born of the same parents OD values) × 100%.
As a result as shown in Figure 1, wogonin can suppress the growth of renal cell carcinoma cell with Sutent.20 μM of Chinese Huangs
A kind of reed mentioned in ancient books element processing 786-O cells are after 48 hours, and compared with not adding drug-treated 786-O cells, cell viability reduces about 15%；
40 μM of wogonins handled 786-O cells after 48 hours, and cell viability reduces about 55%；5 μM of Sutents are handled 48 hours
Afterwards, cell viability reduces about 21%；After 10 μM of Sutents are handled 48 hours, cell viability reduces about 51%；Composition A
After group processing 48 hours, cell viability reduces about 66%, medication combined index CI=0.576；Composition B groups are handled 48 hours
Afterwards, cell viability reduces about 89%, medication combined index CI=0.431；After composition C groups are handled 48 hours, cell viability
Reduce about 97%, medication combined index CI=0.329.Similar with 786-O cells, wogonin also may be used with Sutent processing
The vigor of OS-RC-2 cells is caused to be decreased obviously.Compared with not adding drug-treated OS-RC-2 cells, 20 μM of wogonins
OS-RC-2 cells are handled after 48 hours, cell viability reduces about 10%；40 μM of wogonin processing OS-RC-2 cells 48 are small
Shi Hou, cell viability reduces about 28%；After 5 μM of Sutents are handled 48 hours, cell viability reduces about 17%；10 μM relax
After Buddhist nun is handled 48 hours for Buddhist nun, cell viability reduces about 55%；After composition A groups are handled 48 hours, cell viability is reduced
About 64%, medication combined index CI=0.540；After composition B groups are handled 48 hours, cell viability reduces about 88%, medicine
Association index CI=0.348；After composition C groups are handled 48 hours, cell viability reduces about 95%, medication combined index CI=
0.403。
These results, which show that wogonin is cooperateed with Sutent, can more effectively suppress the growth of kidney cancer cell.And
Concentration dependent is presented in inhibition.
Embodiment 2：Wogonin can more effectively induce renal cell carcinoma cell apoptosis with Sutent composition
This example demonstrates that wogonin is cooperateed with Sutent can more effectively induce renal cell carcinoma cell apoptosis.
In the present embodiment, renal cell carcinoma cell used is people's kidney clear cell adenocarcinoma cell 786-O cells and OS-RC-2 cells.
Experiment packet and administration final concentration are as follows：
Blank control group：The sub- wind (DMSO) of isometric excipient dimethyl
Wogonin group：40 μm of ol/L wogonins
Sutent group：10 μm of ol/L Sutents
Composition A groups：+ 5 μm of ol/L Sutents of 10 μm of ol/L wogonins
Composition B groups：+ 5 μm of ol/L Sutents of 20 μm of ol/L wogonins
Composition C groups：+ 10 μm of ol/L Sutents of 20 μm of ol/L wogonins
One-step method TUNEL cell apoptosis detection kits (red fluorescence) are purchased from (the production of green skies Bioisystech Co., Ltd
Article Number C1089).
TUNEL methods detect Apoptosis：Cell culture be the same as Example 1.Choose exponential phase 786-O and OS-RC-2 thin
Born of the same parents, are separately added into each group drug-treated 48 hours, and PBS is washed one time, add immunostaining fixer room temperature and fix 20 minutes.Abandon solid
Determine liquid, PBS is washed 2 times, add 0.5%TritonX 100 PBS room temperature treatments 30 minutes.Supernatant is abandoned, PBS is washed 2 times, by 20 μ l
The TUNEL dyeing liquors of Fresh are added drop-wise on cell climbing sheet, and 37 DEG C of lucifuges are incubated 60 minutes, and add containing DAPI anti-is quenched
Agent, is taken pictures using fluorescence microscope.
As a result as shown in Fig. 2 untreated 786-O Apoptosis ratio is only about 2%, 40 μM of wogonins are handled 48 hours
Apoptotic cell ratio rises to about 33% afterwards；Apoptotic cell ratio rises to about 43% after 10 μM of Sutents are handled 48 hours；
After composition A groups are handled 48 hours, 786-O Apoptosis ratios are about 56%；After composition B groups are handled 48 hours, cell withers
The ratio of dying is about 79%；After composition C groups are handled 48 hours, Apoptosis ratio is about 91%.
Similar with 786-O cells, untreated OS-RC-2 Apoptosis ratio is only about 3%, 40 μM of wogonin processing 48
OS-RC-2 apoptotic cell ratios rise to 18% after hour；Apoptotic cell ratio rises after 10 μM of Sutents are handled 48 hours
To 46%；After composition A groups are handled 48 hours, OS-RC-2 Apoptosis ratios are about 50%；Composition B groups are handled 48 hours
Afterwards, Apoptosis ratio is about 71%；After composition C groups are handled 48 hours, Apoptosis ratio is about 88%.
These results, which show that wogonin is cooperateed with Sutent, can more effectively induce the apoptosis of renal cell carcinoma cell,
And concentration dependent is presented in inducing effect.
Embodiment 3：Wogonin and the activity that Sutent composition suppresses renal cell carcinoma cell DNA replication dna are higher
This example demonstrates that wogonin cooperateed with Sutent can more effectively suppress renal cell carcinoma cell DNA answer
System.In the present embodiment, the renal cell carcinoma cell is people's kidney clear cell adenocarcinoma cell 786-O and OS-RC-2 cell.
Experiment packet and administration final concentration are as follows：
Blank control group：The sub- wind (DMSO) of isometric excipient dimethyl
Wogonin group：40 μm of ol/L wogonins
Sutent group：10 μm of ol/L Sutents
Composition A groups：+ 5 μm of ol/L Sutents of 10 μm of ol/L wogonins
Composition B groups：+ 5 μm of ol/L Sutents of 20 μm of ol/L wogonins
Composition C groups：+ 10 μm of ol/L Sutents of 20 μm of ol/L wogonins
Cellular immunity dyeing fixer is purchased from green skies Bioisystech Co., Ltd (production number P0098), EdU cells propagation
Detection kit is purchased from Guangzhou Ribo Bio Co., Ltd. (production number C10310-1).Anti- quencher is purchased from
Invitrogen companies (production number P36931).
The propagation detection of EdU cells：Cell culture be the same as Example 1.Choose the OS-RC-2 cells and 786-O of exponential phase
Cell, is separately added into each group medicine, after handling 24 hours, and 37 DEG C, 5%CO are placed on after adding EdU220 points are cultivated in incubator
Clock, PBS one time.Stayed overnight using cellular immunity dyeing 4 DEG C of fixations of fixer, carry out EdU dyeing.Anti- containing DAPI is added to quench
Go out agent, fluorescence microscope is taken pictures.
As a result as shown in figure 3, wogonin can significantly reduce renal cell carcinoma cell EdU incorporation sun with Sutent processing
The ratio of property cell.It is about 38% that drug-treated 786-O cell EdU mixed ratios, which are such as not used, 40 μM of wogonin processing 24
After hour, 786-O cell EdU mixed ratios are reduced to about 18%；After 10 μM of Sutents are handled 24 hours, 786-O cells EdU
Mixed ratio is reduced to about 13%.After composition A groups are handled 24 hours, EdU mixed ratios are reduced to about 12%；Composition B groups
After processing 24 hours, EdU mixed ratios are reduced to about 6%；After composition C groups are handled 24 hours, EdU mixed ratios are reduced to about
1.6%.
Similar therewith, untreated OS-RC-2 cells EdU mixed ratios are about 45%, and 40 μM of wogonins are handled 24 hours
Afterwards, OS-RC-2 cells EdU mixed ratios are reduced to about 31%；After 10 μM of Sutents are handled 24 hours, OS-RC-2 cells EdU
Mixed ratio is reduced to about 27%.After composition A groups are handled 24 hours, EdU mixed ratios are reduced to about 22%；Composition B groups
After processing 24 hours, cell viability is reduced to about 7.5%；After composition C groups are handled 24 hours, EdU mixed ratios are reduced to about
3%.
These results show that wogonin cooperates with the DNA that can more effectively suppress renal cell carcinoma cell to answer with Sutent
Ability processed, and concentration dependent is presented in inhibition.
Embodiment 4：Wogonin can effectively suppress Sutent drug resistance renal cell carcinoma cell with Sutent composition
Propagation
This example demonstrates that wogonin is cooperateed with Sutent can effectively suppress Sutent drug resistance nephrocyte
The propagation of cancer cell.In the present embodiment, the renal cell carcinoma cell is people's kidney clear cell adenocarcinoma cell 786-O and OS-RC-
2 cells.
Experiment packet and administration final concentration are as follows：
Blank control group：The sub- wind (DMSO) of isometric excipient dimethyl
Wogonin low dose group：20 μm of ol/L wogonins
Wogonin high dose group：40 μm of ol/L wogonins
Sutent low dose group：5 μm of ol/L Sutents
Sutent high dose group：10 μm of ol/L Sutents
Composition of medicine group：+ 40 μm of ol/L wogonins of 10 μm of ol/L Sutents
The foundation of Sutent resistance renal cancer cell line：The OS-RC-2 cells and 786-O cells of exponential phase are chosen,
Cell culture medium uses RPMI-1640 culture mediums (Gibco companies of the U.S., production number containing 10 μm of ol/L Sutents
11875127) 10% (V/V) hyclone of addition (Gibco companies of the U.S., (production number 1099141), and add 100U/ml's
Penicillin and 100mg/ml streptomysins, with 37 DEG C, CO2Partial pressure is passed on more than 10 times for the CMC model of 5% (percentage by volume),
The cell of acquisition is Sutent drug-resistant cell strain.
Tetrazolium bromide (MTT) tests be the same as Example 1.
As a result as shown in Figure 4,5 μm of ol/L Sutent low dosage treatment group 786-O Sutent mdr cell vigor with
Blank control group is compared without significant difference, and 10 μm of ol/L Sutent high dose treatment group 786-O Sutents mdr cells are lived
Power only have dropped 10% compared with blank control group, show Sutent resistance 786-O cells to Sutent processing not
It is sensitive；By comparison, after 20 μM of wogonins are handled 48 hours, 786-O cell viabilities reduce about 13%；40 μM of wogonins
After processing 48 hours, 786-O cell viabilities reduce about 37%；After composition of medicine group is handled 48 hours, cell viability is reduced
About 72%, medication combined index CI=0.671.Similar with 786-O cells, Sutent low dosage treatment group OS-RC-2 relaxes Buddhist nun
For Buddhist nun's mdr cell vigor compared with blank control group without significant difference, Sutent high dose treatment group OS-RC-2 Buddhist nuns of relaxing replace
Buddhist nun's mdr cell vigor only have dropped 11% compared with blank control group, show Sutent resistance OS-RC-2 cells to relaxing
Buddhist nun is handled and insensitive for Buddhist nun；By comparison, after 20 μM of wogonins are handled 48 hours, OS-RC-2 cell viabilities are reduced about
8%；After 40 μM of wogonins are handled 48 hours, OS-RC-2 cell viabilities reduce about 26%；Composition of medicine group is handled 48 hours
Afterwards, cell viability reduces about 64%, medication combined index CI=0.63.
These results, which show that wogonin is cooperateed with Sutent, can effectively overcome renal cell carcinoma cell to Sutent
Drug resistance.
Embodiment 5：Wogonin can effectively induce Sutent drug resistance renal cell carcinoma cell with Sutent composition
Apoptosis
This example demonstrates that wogonin is cooperateed with Sutent can effectively induce Sutent drug resistance nephrocyte
The apoptosis of cancer cell.In the present embodiment, the renal cell carcinoma cell is people's kidney clear cell adenocarcinoma cell 786-O and OS-RC-
2 cells.
Experiment packet and administration final concentration are as follows：
Blank control group：The sub- wind (DMSO) of isometric excipient dimethyl
Wogonin group：40 μm of ol/L wogonins
Sutent group：10 μm of ol/L Sutents
Composition of medicine group：+ 40 μm of ol/L wogonins of 10 μm of ol/L Sutents
The foundation of Sutent resistance renal cancer cell line：Be the same as Example 4.
TUNEL methods detect Apoptosis：Be the same as Example 2.Choose exponential phase Sutent resistance 786-O and OS-RC-
2 cells, are separately added into each group drug-treated and TUNEL methods detection Apoptosis are carried out after 48 hours.
As a result as shown in figure 5, Sutent treatment group 786-O Sutents mdr cell apoptosis ratio and blank control group
Compared to without significant difference, apoptotic cell ratio rises to about 31% after 40 μM of wogonins are handled 48 hours；At composition of medicine group
Reason is after 48 hours, and 786-O Sutent mdr cell apoptosis ratios rise to about 67%.
It is similar with 786-O cells, Sutent treatment group OS-RC-2 Sutent mdr cell vigor and blank control group
Compared to without significant difference, OS-RC-2 Sutent mdr cell apoptosis ratios rise to after 40 μM of wogonins are handled 48 hours
26%；After composition of medicine group is handled 48 hours, OS-RC-2 Sutent mdr cell apoptosis ratios rise to about 53%.
These results, which show that wogonin is cooperateed with Sutent, can effectively reverse Sutent resistance clear-cell carcinoma
Anti-apoptotic activities of the cell to Sutent.
Embodiment 6：Wogonin can effectively suppress Sutent drug resistance renal cell carcinoma cell with Sutent composition
DNA replication dna.
This example demonstrates that wogonin can effectively suppress Sutent drug resistance clear-cell carcinoma with Sutent composition
The DNA replication dna of cell.In the present embodiment, the renal cell carcinoma cell is people's kidney clear cell adenocarcinoma cell 786-O and OS-
RC-2 cells.
Experiment packet and administration final concentration are as follows：
Blank control group：The sub- wind (DMSO) of isometric excipient dimethyl
Wogonin group：40 μm of ol/L wogonins
Sutent group：10 μm of ol/L Sutents
Composition of medicine group：+ 40 μm of ol/L wogonins of 10 μm of ol/L Sutents
The foundation of Sutent resistance renal cancer cell line：Be the same as Example 4.
EdU detection cell propagation：Be the same as Example 3.
786-O the and OS-RC-2 Sutent mdr cells of exponential phase are chosen, each group medicine is separately added into, handled
After 24 hours, EdU detections are carried out.
As a result as shown in fig. 6, the positive ratio of Sutent treatment group 786-O Sutent mdr cells EdU incorporations and sky
White control group is compared without significant difference, after 40 μM of wogonins are handled 24 hours, 786-O Sutent mdr cells EdU incorporations
Ratio is reduced to about 22%；After composition of medicine group is handled 24 hours, EdU mixed ratios are reduced to about 13%；
It is similar therewith, the positive ratio of Sutent treatment group OS-RC-2 Sutent mdr cells EdU incorporations and blank pair
Compared according to group without significant difference, after 40 μM of wogonins are handled 24 hours, OS-RC-2 cell EdU mixed ratios are reduced to about
33%；After composition of medicine group is handled 24 hours, EdU mixed ratios are reduced to about 21%.
These results, which show that wogonin is cooperateed with Sutent, can effectively suppress Sutent resistance clear-cell carcinoma
The DNA replication dna ability of cell.
Present embodiments are exemplarily illustrated above in association with accompanying drawing.Those skilled in the art are according to this specification
Disclosure is readily apparent that, each embodiment suitably can be adjusted and reconfigured according to actual needs,
Without departing from spirit herein.The protection domain of the application is defined by following claims.
Claims (10)
1. the application of Sutent and wogonin composition in treatment clear-cell carcinoma medicine is prepared.
2. a kind of pharmaceutical composition for treating clear-cell carcinoma, it is characterised in that including：Sutent and wogonin.
3. composition as claimed in claim 2, it is characterised in that the mol ratio of the Sutent and wogonin is 1:(1
~10)；
It is preferred that, the mol ratio of the Sutent and wogonin is 1:(1~8)；It is further preferred that the Sutent
Mol ratio with wogonin is 1:(4~8)；
It is preferred that, the quality of the Sutent and wogonin accounts for the 1~99.5% of described pharmaceutical composition.
4. composition as claimed in claim 2, it is characterised in that also including pharmaceutically acceptable excipient.
5. composition as claimed in claim 2, it is characterised in that the mol ratio of the Chinese Sutent and baicalein is 1: 1
~9,1:1~8,1:1~7,1:1~6,1:1~5,1:1~4,1:1~3,1:1~2,1:2~10,1:2~9,1:2~8,1:
2~7,1:2~6,1: 2~5,1:2~4,1:2~3,1:3~10,1:3~9,1:3~8,1:3~7,1:3~6,1:3~5,
1:3~4,1:4~10,1:4~9,1:4~8,1:4~7,1:4~6,1:4~5,1:5~10,1:5~9,1:5~8,1:5~
7、1:5~6,1:6~10,1:6~9,1: 6~8,1: 6~7,1: 7~10,1: 7~9,1: 7~8,1: 8~10,1: 8~9 and
1: 9~10；
It is preferred that, the mol ratio of the Sutent and wogonin is 1: 6~10；
It is further preferred that the mol ratio of the Sutent and wogonin is 1: 8~10.
6. a kind of medicine box, it is characterised in that including：Wogonin and Sutent.
7. medicine box as claimed in claim 6, it is characterised in that the mol ratio of the Sutent and wogonin is 1: (1~
10)；
It is preferred that, the mol ratio of the Sutent and wogonin is 1: (1~8)；It is further preferred that the Sutent
Mol ratio with wogonin is 1: (4~8).
8. medicine box as claimed in claim 6, it is characterised in that the quality of the Sutent and wogonin accounts for the medicine
The 1~99.5% of composition.
9. medicine box as claimed in claim 6, it is characterised in that described Sutent and the quality of wogonin account for the medicine
1~99%, 1~90%, 1~80%, 1~70%, 1~60%, 1~50%, 1~40%, the 1 of compositions or medicine box quality
~30%, 1~20%, 1~10%, 10~99.5%, 10~99%, 10~90%, 10~80%, 10~70%, 10~
60%th, 10~50%, 10~40%, 10~30%, 10~20%, 20~99.5%, 20~99%, 20~90%, 20~
80%th, 20~70%, 20~60%, 20~50%, 20~40%, 20~30%, 30~99.5%, 30~99%, 30~
90%th, 30~80%, 30~70%, 30~60%, 30~50%, 30~40%, 40~99.5%, 40~99%, 40~
90%th, 40~80%, 40~70%, 40~60%, 40~50%, 50~99.5%, 50~99%, 50~90%, 50~
80%th, 50~70%, 50~60%, 60~99.5%, 60~99%, 60~90%, 60~80%, 60~70%, 70~
99.5%th, 70~99%, 70~90%, 70~80%, 80~99.5%, 80~99%, 80~90%, 90~99.5% or 90
~99%.
10. medicine box as claimed in claim 6, it is characterised in that described Sutent and the quality of wogonin account for described
Pharmaceutical composition or medicine box quality 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%,
13%th, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%,
28%th, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%,
43%th, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%,
58%th, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%,
73%th, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%,
88%th, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5%.
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| CN111110851A (en) * | 2020-01-20 | 2020-05-08 | 哈尔滨商业大学 | Pharmaceutical composition of baicalein and tyrosine kinase inhibitor and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973550A (en) * | 2011-09-05 | 2013-03-20 | 谢秀梅 | Pharmaceutical composition for inhibiting cancer stem cell growth or cancer cell metastasis by using wogonin, and application thereof |
-
2017
- 2017-06-14 CN CN201710448010.5A patent/CN107198685B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102973550A (en) * | 2011-09-05 | 2013-03-20 | 谢秀梅 | Pharmaceutical composition for inhibiting cancer stem cell growth or cancer cell metastasis by using wogonin, and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| LI WEN RONG等: "Combination of wogonin and sorafenib effectively kills human hepatocellular carcinoma cells through apoptosis potentiation and autophagy inhibition", 《ONCOLOGY LETTERS》 * |
| 寿建忠等: "肾癌的靶向治疗现状与进展", 《中国新药杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111110851A (en) * | 2020-01-20 | 2020-05-08 | 哈尔滨商业大学 | Pharmaceutical composition of baicalein and tyrosine kinase inhibitor and application thereof |
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