CN108113987A - Ion pump inhibitor inhibits the purposes in Epithelial and stromal conversion and anti-tumor metastasis - Google Patents
Ion pump inhibitor inhibits the purposes in Epithelial and stromal conversion and anti-tumor metastasis Download PDFInfo
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- CN108113987A CN108113987A CN201810008198.6A CN201810008198A CN108113987A CN 108113987 A CN108113987 A CN 108113987A CN 201810008198 A CN201810008198 A CN 201810008198A CN 108113987 A CN108113987 A CN 108113987A
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- MCISBLIDHPXZEW-UHFFFAOYSA-N CC(CCCC1C)C=C1N=C(N)S(CC(NC)=CC)O Chemical compound CC(CCCC1C)C=C1N=C(N)S(CC(NC)=CC)O MCISBLIDHPXZEW-UHFFFAOYSA-N 0.000 description 1
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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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
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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Abstract
The present invention provides a kind of purposes of ion pump inhibitor in Epithelial and stromal conversion and anti-tumor metastasis is inhibited.The general structure of the ion pump inhibitor is as follows：The effective concentration of the ion pump inhibitor is 10 μM of 20nM.The present invention utilizes the screening technique of high-efficiency dynamic, a variety of micromolecular compounds are made whether be EMT target spots screening, Epithelial and stromal conversion and metastases can effectively be inhibited by obtaining ion pump inhibitor, therapy target to be clinically used to treat metastases provides new method, can bring huge social and economical benefits.
Description
Technical field
The present invention relates to pharmaceutical technology fields, specifically, are related to a kind of ion pump inhibitor and inhibit Epithelial and stromal conversion
And the purposes in anti-tumor metastasis.
Background technology
With the high speed development of global economy humanities of science, the mankind will more and more concern eyes be placed on Global Health this
On a theme.A variety of diseases such as statistical analysis, ischemic heart disease, cerebrovascular disease are carried out to global disease burden according to CBD in 2015
Disease threatens the kinds cancers such as human health, wherein lung cancer, liver cancer, colon cancer, breast cancer to be also in list, becomes that the mankind are No.1 to be killed
One of hand.From there is explicitly defining by now for cancer, either government organs, scientific research personnel or non-government organization's input are tens of
Year, cancer is captured to which cancer Mysterious Veil can be opened, but is arrived a few days ago, with economic development, population built-up, the morbidity of cancer
High situation is still presented in rate, lethality.It is counted according to GLOBOCAN, the newly-increased cases of cancer 1406.8 ten thousand in the whole world in 2012,
820.2 ten thousand people die of cancer, and 3245.5 ten thousand people band knurl in 5 years is survived.It is only Chinese, it is single just to have within 2012 306.5 ten thousand newly-increased cancers
Disease case, 2,200,000 people die of cancer.Therefore research and development are very urgent for the effective therapy of cancer.
Current clinic is still based on surgical excision for the treatment of solid tumor, is aided with radiation and chemotherapy and is free on to kill
Blood vessel, potential metastatic lesion or the remaining tumour cell of stove in situ.Chemicotherapy mechanism of action be by cytotoxic compound and
Radioactive ray come inhibit tumor cell proliferation so as to achieve the purpose that kill tumour cell.Radiotherapy chemotherapy gimmick due to its mechanism of action,
The normal cell in cell proliferation period also has lethal effect, therefore toxic side effect is larger.Compared to the low specificity of chemicotherapy,
The birth of molecular targeted compound is then for efficiently precisely targeting therapy on tumor brings new vigor.Tumour chemical combination as a new generation
Object, molecular targeted compound are capable of the signal path or biological processes of specific effect abnormal activation in tumour cell, with
Traditional Radiotherapy chemotherapy is compared to more efficient, less side effects.
Tumor invasion position is varied, and grade malignancy and the death rate are also had nothing in common with each other, but tumor lethal reason is still
It can be summarized as at following 4 points：1. concurrent infection.Tumor patient hypoimmunity causes secondary severe infections even dead；2. battalion
It supports and exhausts, metabolism is not normal.Tumour cell is adjusted compared to normal cell from Aging mechanism, is proliferated quick consumption macrometabolic element
Matter, and therefore it is metabolized not normal, Metabolite Accumulation.3. abnormal bleeding；4. metastases.Metastases to other important organs,
Dystopy abnormality proliferation causes related organ function damage even failure, causes death so as to destroy internal organs normal physiological structure.And
Among this some cause of death, 90% tumor mortality case dies of metastases.Metastases are the main lifes of malignant tumour
One of object characteristic, tumour cell departs from primary tumo(u)r stove, and via blood vessel, the approach such as lymphatic or body cavity reach distal end
Other positions regrow to form secondary transfer stove.
Among solid tumor, polymorphism is presented in tumour cell, and the existing cell in differentiation epithelium state completely also has point
The relatively low interstitial state cell of change degree, the cell of different conditions have each different characteristics.The cell of epithelium state is rich in thin
Born of the same parents' polarity, iuntercellular arrangement are close-coupled on extracellular basilar memebrane, expression cell adhesion molecule (such as cadherin E-
Cadherin), and the cell of interstitial state is then no cell polarity, be not connected with extracellular basilar memebrane, it is migration, invasion and attack, thin
Born of the same parents' dynamic role is high, and cell does not express either a small amount of expression cell adhesion molecule and great expression vimentin Vimentin.
In in situ tumor, most of tumour cell is existed in the form of epithelium state.If tumour cell needs to attack, diffuse to remote
End tissue then develops to form transfer stove, and neoplastic epithelial cells just need transformation into the state of more interstitial phenotype.This turn
Becoming needs a kind of cell biology process of complexity to participate in, i.e. Epithelial and stromal conversion (Epithelial-Mesenchymal
transition,EMT).During generation EMT, epithelial tumor cell loses cell adherence, cell memory and the spy for lacking dynamic role
Property, obtain dynamic role, the interstitial characteristic of invasive ability and stem-like cell.EMT is a dynamic process, is also existed in organism
MET processes on the other side, i.e. mesenchymal epithelium convert, and cell loss interstitial phenotypic characteristic is transformed into epithelial phenotype characteristic, so as to
Reduce the probability that cell invasion goes out in situ tumor.Played the part of based on EMT during tumor development and Malignant tumor of bonal metastasis
The key player drilled, it will be that oncotherapy brings new contract to explore molecular targeted compound of the research and development based on EMT or MET
Machine.
Ion pump inhibitor (proton pump inhibitors, abbreviation PPIs) is that one kind is mainly used for long-acting persistently subtracting
The drug of few gastric acid secretion, clinical indication are mainly that indigestion, peptic ulcer etc. is enterogastric diseases.Ionic pump inhibits
Agent is one of widest solid-state drug of global marketing (" WHO Model List of EssentialMedicines " .World
Health Organization.October 2013).Ion pump inhibitor includes：Lansoprazole (Lansoprazole), Austria
U.S. draws azoles (Omeprazole), Dexlansoprazole (Dexlansoprazole), esomeprazole (Esomeprazole), dissolves
Support draws azoles (Pantoprazole), Rabeprazole (Rabeprazole), Iprazole (Ilaprazole).
The content of the invention
The technical problem to be solved by the present invention is in view of the shortcomings of the prior art, provide in a kind of ion pump inhibitor inhibition
Purposes in skin mesenchymal transformation and anti-tumor metastasis.
The molecular targeted compound based on EMT or MET, this hair are filtered out from numerous micromolecular compounds in order to realize
It is bright to make use of a kind of double chemiluminescent Reporter systems as the biological process converted based on Epithelial and stromal to screen targeting EMT's
Compound captures metastases to realize, treats the clinical value of tumour.
This pair of chemiluminescent Reporter system is designed based on the variation of key protein expression quantity in Epithelial and stromal conversion.
In the cell for surely having turned this report system, when cell is in epithelial phenotype expression cadherin Ecadherin, cell can express
Firefly luciferase Luciferase；When cell is in interstitial phenotypic expression vimentin Vimentin, cell then can table
Up to renilla luciferase Renilla；And the intermediate state in epithelium and interstitial, i.e., existing Ecadherin expression have again
When Vimentin is expressed, cell then expresses fluorescent luciferase and renilla luciferase simultaneously.Both luciferases can be made
For different substrates and generate fluorescence signal and quantitatively detected by chemiluminescence detector.According to the principle of reporting system, in phase
On the basis of cell quantity, such as plus the experimental group luciferase readings of compound raise, then MET occurs；Conversely, work as
When luciferase readings reduce, then EMT occurs.It is screened by a series of experiments, it is of the invention from more than 1200 kinds of small molecule chemical combination
Screening finds that ion pump inhibitor can efficiently inhibit the small molecule that EMT occurs for cell in object.
The purpose of the present invention is what is be achieved through the following technical solutions：
The present invention provides a kind of purposes of ion pump inhibitor in Epithelial and stromal conversion and anti-tumor metastasis is inhibited.
Preferably, the general structure of the ion pump inhibitor is as follows：
Preferably, the ion pump inhibitor be selected from Lansoprazole, Omeprazole, Dexlansoprazole, esomeprazole,
Pantoprazole, Rabeprazole, Iprazole.Structural formula is as follows：
Lansoprazole (Lansoprazole)
Omeprazole (Omeprazole)
Dexlansoprazole (Dexlansoprazole)
Esomeprazole (Esomeprazole)
Pantoprazole (Pantoprazole)
Rabeprazole (Rabeprazole)
Iprazole (Ilaprazole)
Preferably, the effective concentration of the ion pump inhibitor is 20nM-10 μM.
The present invention also provides a kind of ion pump inhibitors to prepare the conversion of inhibition Epithelial and stromal and medicine for anti transfer of tumor
Purposes in composition.
Preferably, the ion pump inhibitor be selected from Lansoprazole, Omeprazole, Dexlansoprazole, esomeprazole,
Pantoprazole, Rabeprazole, Iprazole.
Preferably, in described pharmaceutical composition, the effective concentration of ion pump inhibitor is 20nM-10 μM.
Preferably, described pharmaceutical composition further includes pharmaceutically acceptable carrier or excipient.
Preferably, described pharmaceutical composition further includes other antitumor drugs.
Preferably, other described antitumor drugs include taxol.
Compared with prior art, the present invention has following advantageous effect：
The present invention utilize high-efficiency dynamic screening technique, a variety of micromolecular compounds are made whether be EMT target spots sieve
Choosing, Epithelial and stromal conversion and metastases can effectively be inhibited by obtaining ion pump inhibitor, clinically to turn for treating tumour
The therapy target of shifting provides new method, can bring huge social and economical benefits.
Description of the drawings
Upon reading the detailed description of non-limiting embodiments with reference to the following drawings, other feature of the invention,
Objects and advantages will become more apparent upon：
Fig. 1：Double fluorescence and double chemiluminescent Reporter system plasmid schematic diagrames；
Fig. 2:Double chemiluminescent Reporter system effectiveness result figures are verified using TGF-β；Wherein, Fig. 2 a are addition TGF-β
The ratio of luciferase (Ecadherin) and Renilla luciferase (Vimentin) raises afterwards；Fig. 2 b are addition
Luciferase (Ecadherin) reading raises after TGF-β；Fig. 2 c are Renilla luciferase after addition TGF-β
(Vimentin) reading reduces；
Fig. 3：Micromolecular compound storehouse the selection result；
Fig. 4：Micromolecular compound concentration dependant result；
Fig. 5：Micromolecular compound concentration dependant result；
Fig. 6：Ion pump inhibitor testing result；
Fig. 7：Lansoprazole scratch experiment result；Wherein, when Fig. 7 a are control group DMSO cut 0h；Fig. 7 b are control group
DMSO cuts for 24 hours when；When Fig. 7 c are control group DMSO cut 40h；When Fig. 7 d are experimental group Lansoprazole cut 0h；Fig. 7 e are real
When testing group Lansoprazole cut for 24 hours；When Fig. 7 f are experimental group Lansoprazole cut 40h；Fig. 7 g move for control group experimental group cell
Move area statistics result；
Fig. 8：Lansoprazole transwell experimental results；Wherein, Fig. 8 a be control group DMSO cell for 24 hours after at 10 times
Cell migration situation under object lens；Fig. 8 b be control group DMSO cell for 24 hours after under 20 times of object lens cell migration situation；Fig. 8 c are
The cell of experimental group Lansoprazole for 24 hours after under 10 times of object lens cell migration situation；Fig. 8 d are the cell of experimental group Lansoprazole
After for 24 hours under 20 times of object lens cell migration situation；Fig. 8 e be the cell of control group DMSO and experimental group Lansoprazole after 24h
Migrating cell quantity statistics；
Fig. 9：Lansoprazole balling-up experimental result；Wherein, Fig. 9 a are control group DMSO balling-up effects under 4 times of object lens；Figure
9b is control group DMSO balling-up effects under 20 times of object lens；Fig. 9 c are experimental group Lansoprazole balling-up effect under 4 times of object lens；Figure
9d is experimental group Lansoprazole balling-up effect under 20 times of object lens；Fig. 9 e are control group experimental group balling-up quantity statistics result；
Wherein, * * * represent p<0.001, * * represents p<0.01, * represents p<0.05, experimental result be expressed as average value ±
S.E.M。
Specific embodiment
With reference to specific embodiment, the present invention is described in detail.Following embodiment will be helpful to the technology of this field
Personnel further understand the present invention, but the invention is not limited in any way.It should be pointed out that the ordinary skill to this field
For personnel, without departing from the inventive concept of the premise, several changes and improvements can also be made.These belong to the present invention
Protection domain.
Embodiment 1
Experiment material and equipment：PC3 cell lines (CRL-1435TM),(Cat no114-07), it is double
Chemiluminescent Reporter system (pLenti-EcadPm-mCherry-PA-Spacer-VimPm-eGFP-PA-hPKG-Puro) is small
Molecular compound storehouse (Tao Su).
Experimental procedure：
1. the double chemiluminescence systems of transfection simultaneously verify work efficiency
1.1 are uniformly inoculated into human prostate cancer cell line PC3 single cell suspensions in six orifice plates, treat cell growth to density
For 80% or so when, use(Cat no114-07) transfection reagent is by double fluorescence report system pLenti-EcadPm-
MCherry-PA-Spacer-VimPm-eGFP-PA-hPKG-Puro (Fig. 1) is transfected into PC3 cells, specific transfection method ginseng
It examinesTransfection reagent operating instruction.
1.2 transfection 72 it is small when after, micro- Microscopic observation cell state adds 1ug/ in the medium when cell state is good
The puromycin of ml carries out cell screening.
After when 1.3 puromycins screening 48 is small, cell state is stablized, and when cell growth to density is 90%, uses pancreatin
Single cell suspension is digested to, and is uniformly seeded in 24 orifice plates.It treats that cell attachment is complete, is sent out to double fluorescence have been transfected with double chemistry
In the cell of photosystem plus 100ng/ml TGF-β so that EMT occurs for cell, and when TGF-β processing 72 is small after carry out chemistry
Shine detection luciferase and Renilla signal ratios (Fig. 2), is control group Ctrl without TGF β processing group.
2. surely turn cell line selection micromolecular compound storehouse
2.1 (are sieved using the PC3 cell lines for surely having turned double chemiluminescent Reporter systems through the puromycin in step 1.3
Select 48 it is small when after, cell state stablize), when cell growth to density be 90% when, be digested to single cell suspension with pancreatin, press
The density of 1000 cells/wells is seeded in special 96 orifice plates (Fluidx, 66-42049-L) of chemiluminescence detection.Small molecule
Each compound is single in drug reservoir is set to an experimental group, and each experimental group sets up 3 secondary orifices, and every piece of 96 orifice plates set up one
Negative control group (addition solvent DMSO), a positive controls (addition 100ng/ml TGF-β).
2.2 experimental group compound concentrations are 10 μM, change a subculture every three days, after compound is handled 7 days, detect and divide
Analyse data.
2.3CCK8 detect every group of cell quantity variation.Each orifice plate removal supernatant, is washed one time with PBS.After discarding PBS, add
Add 100ul complete mediums, and by per 100ul culture medium 10ul CCK8 reagents standard addition CCK8 (colleague, cck8-kit,
CK08).When 37 DEG C of incubator effects 2 are small, microplate reader absorbs luminous intensity in 450nm wavelength detectings.
2.4 discard cck8 effect liquid, are washed twice with PBS so that disturbed without color.After discarding PBS, Promega is used
ONE-GloTMLuciferase assay system (E6110) carry out chemiluminescent detection.Specific transfection method reference
Promega companies ONE-GloTMLuciferase assay system detection reagent operating instructions.Detecting instrument：Promega is public
DepartmentDiscover System, software program are the ONE-Glo that instrument carriesTMluciferase assay system
Detection architecture.
2.5 analysis result.The light absorption value detected with CCK8 kits represents cell quantity in each group, luciferase
Reading represents the expression of the Ecadherin of each group cell.With cell quantity band between each hole of extinction numerical value equalization
The luciferase reading differences come, so as to judge whether the compound makes cell by the height of luciferase readings
The expression quantity of Ecadherin changes.The results show that TGF-β can promote cell that EMT occurs, i.e., so that luciferase/
The reading of cck8 reduces.As a result such as Fig. 3.
2.6 pick out so that after the raised compound of luciferase/cck8 readings, set more concentration gradients, inspection
It surveys compound and so that cell occurs whether MET is concentration dependant.Specific experiment operates same step 1) -5), concentration gradient is 10 μM,
1 μM, 100nM.As a result such as Fig. 4, the reading of luciferase/cck8 are raised with the rise of concentration.
2.7 to pick out concentration dependant with obvious effects, and luciferase/cck8 ratios raise apparent compound, expand dense
Gradient is spent, specific experiment operates same step 1) -5), concentration gradient is 10 μM, 5 μM, 1 μM, 100nM, 20nM.As a result such as Fig. 5,
In there are three compound concentration dependant after concentration gradient is expanded effect it is very good.And wherein No. six compound be from
The reading of the luciferase/cck8 of one of sub- pump inhibitor Lansoprazole is raised with the rise of concentration.
2.8 analysis of compounds types find that ion pump inhibitor Lansoprazole lansoprazole works well.Buy it
The ion pump inhibitor of his remaining species is using double chemiluminescent Reporter systems and with same procedure detection ion pump inhibitor
It is no to cause cell that MET occurs.The result is shown in Fig. 6, ion pump inhibitor can cause the reading liter of cell luciferase/cck8
It is high.
3. ion pump inhibitor biological function verification
The Lansoprazole (Lansoprazole) selected in ion pump inhibitor carries out biological function verification
3.1 scratch experiment Wound healing assay
PC3 single cell suspensions prepared by abovementioned steps 1 are by 1*105Even density is seeded in six orifice plates, treats that cell is given birth to
It is long to it is close be 100% when, stayed overnight with the DMEM medium cultures without serum.24 it is small when after, mark straight line with 200ul pipette tips,
Form wound.The culture solution containing floating cells is discarded, the plasma-free DMEM medium containing 10 μM of Lansoprazoles is added, 0
Hour, 24 it is small when, 48 take pictures when small observation wound healing degree.Picture is not healed areal calculation with Image J.As a result such as
Fig. 7, after adding compound of Lansoprazole so that speed of wound healing slows down, i.e., the transfer ability of cell reduces.
3.2 Transwell are tested
After excluding the influence that cell increases when PC3 cells Nature enemy 24 prepared by abovementioned steps 1 is small, it is digested to slender
Born of the same parents, it is 1*10 to be resuspended with the DMEM culture mediums without serum into density6Single cell suspension.Transwell adds 500ul in hole
DMEM culture mediums containing 10%FBS, and add 100ul PC3 cell suspensions in each transewell cells.37 DEG C of cultures, 24
Cell is taken out after hour, the culture medium in cell is discarded, is put into 4% paraformaldehyde and fixes 15min.PBS is rinsed for several times, uses cotton
Label gently wipe the possible remaining cell of cell internal layer away, and cell is placed in crystal violet and dyes 20min.PBS is rinsed for several times, is used
Cotton swab gently wipes uncalled crystal purple dye and PBS.After being dried after cell, cell quantity is observed and recorded under the microscope.Knot
Fruit such as Fig. 8.After adding compound of Lansoprazole, migrate to the cell quantity reduction of cell lower floor, the transfer ability of cell reduces.
3.3 balling-up are tested
By PC3 cell dissociations prepared by abovementioned steps 1 into unicellular, after cell count, by the density of 1000 cells/wells
With Matrigel (BD Growth Factor Reduced Matrigel, 354230) 1:1 is uniformly mixed, volume 200ul,
It is added along orifice plate wall.Be put into incubator it is fixed, 2 it is small when after add culture medium.A subculture is changed within 3 days, processing is taken pictures after 7 days
And count balling-up quantity.Culture medium is：DMEM/F12,2%B27, EGF, FGF.As a result such as Fig. 9.Add compound of Lansoprazole
Afterwards, balling-up population size significantly reduces, and cells switch is reduced into epithelial phenotype stem cell-like properties.
Specific embodiments of the present invention are described above.It is to be appreciated that the invention is not limited in above-mentioned
Particular implementation, those skilled in the art can make a variety of changes or change within the scope of the claims, this not shadow
Ring the substantive content of the present invention.In the case where there is no conflict, the feature in embodiments herein and embodiment can arbitrary phase
Mutually combination.
Claims (9)
1. a kind of purposes of ion pump inhibitor in Epithelial and stromal conversion and anti-tumor metastasis is inhibited.
2. purposes according to claim 1, which is characterized in that the ion pump inhibitor is selected from Lansoprazole, Aomei is drawn
Azoles, Dexlansoprazole, esomeprazole, Pantoprazole, Rabeprazole, Iprazole.
3. purposes according to claim 1, which is characterized in that the effective concentration of the ion pump inhibitor is 20nM-10 μ
M。
4. a kind of ion pump inhibitor is preparing the purposes in inhibiting Epithelial and stromal conversion and medicine for anti transfer of tumor composition.
5. purposes according to claim 4, which is characterized in that the ion pump inhibitor is selected from Lansoprazole, Aomei is drawn
Azoles, Dexlansoprazole, esomeprazole, Pantoprazole, Rabeprazole, Iprazole.
6. purposes according to claim 4, which is characterized in that in described pharmaceutical composition, ion pump inhibitor it is effective
Concentration is 20nM-10 μM.
7. purposes according to claim 4, which is characterized in that described pharmaceutical composition further includes pharmaceutically acceptable load
Body or excipient.
8. purposes according to claim 4, which is characterized in that described pharmaceutical composition further includes other antitumor drugs.
9. purposes according to claim 8, which is characterized in that other described antitumor drugs include taxol.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810008198.6A CN108113987A (en) | 2018-01-04 | 2018-01-04 | Ion pump inhibitor inhibits the purposes in Epithelial and stromal conversion and anti-tumor metastasis |
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| CN201810008198.6A CN108113987A (en) | 2018-01-04 | 2018-01-04 | Ion pump inhibitor inhibits the purposes in Epithelial and stromal conversion and anti-tumor metastasis |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110522752A (en) * | 2019-08-19 | 2019-12-03 | 庹必光 | Application of the Pantoprazole in the drug of preparation prevention and treatment liver fibrosis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008090355A2 (en) * | 2007-01-24 | 2008-07-31 | Procure Therapeutics Limited | Inhibitors of stem cells markers |
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2018
- 2018-01-04 CN CN201810008198.6A patent/CN108113987A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008090355A2 (en) * | 2007-01-24 | 2008-07-31 | Procure Therapeutics Limited | Inhibitors of stem cells markers |
Non-Patent Citations (5)
| Title |
|---|
| BIN ZHANG 等: "Proton pump inhibitor pantoprazole abrogates adriamycin-resistant gastric cancer cell invasiveness via suppression of Akt/GSK-β/β-catenin signaling and epithelial–mesenchymal transition", 《CANCER LETTERS》 * |
| SHUITU FENG 等: "Proton pump inhibitor pantoprazole inhibits the proliferation,self‑renewal and chemoresistance of gastric cancer stem cells via the EMT/β‑catenin pathways", 《ONCOLOGY REPORTS》 * |
| 刘吉龙 等: "质子泵抑制剂抗胃癌的研究进展", 《医学综述》 * |
| 宋嘉 等: "质子泵抑制剂泮托拉唑钠抑制肺癌细胞上皮间质转化和顺铂耐药的基质研究", 《中国病理生理杂志》 * |
| 李亚楠 等: "上皮间质转化抑制剂及其在抗肿瘤治疗中的应用", 《中国生物化学与分子生物学报》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110522752A (en) * | 2019-08-19 | 2019-12-03 | 庹必光 | Application of the Pantoprazole in the drug of preparation prevention and treatment liver fibrosis |
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