CN110882267A - Application of natural product monomer in preparation of anti-tumor metastasis drugs - Google Patents
Application of natural product monomer in preparation of anti-tumor metastasis drugs Download PDFInfo
- Publication number
- CN110882267A CN110882267A CN201911262554.8A CN201911262554A CN110882267A CN 110882267 A CN110882267 A CN 110882267A CN 201911262554 A CN201911262554 A CN 201911262554A CN 110882267 A CN110882267 A CN 110882267A
- Authority
- CN
- China
- Prior art keywords
- compound
- natural product
- cells
- metastasis
- tumor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, and particularly relates to an application of a natural product monomer in preparation of an anti-tumor metastasis medicine. The natural product monomer is a compound shown in the formula I, and the compound containing the structure of the compound shown in the formula I can inhibit the metastasis of tumor cells in different modes, remarkably influence the recombination of cytoskeletal proteins and inhibit lymph node metastasis, and improve the inhibition effect on various tumor cells.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an application of a natural product monomer in preparation of an anti-tumor metastasis medicine.
Background
Tumor metastasis is an important biological feature of malignant tumors, with over 90% of patients with tumors dying and distant metastasis.
Tumor metastasis is a continuous, progressive, dynamic process whose basic process is: the proliferation of primary tumor cells and the rapid growth of new blood vessels around and in the tumor; a few tumor cells invade blood vessels and lymphatic vessels after falling off from primary focuses, and migrate to another part along with blood and lymphatic flow in the circulatory system; the tumor cells are adhered to the wall of the capillary vessel and form a micro metastasis after penetrating out of the vessel; the cells proliferate and generate new blood vessels, forming secondary tumors. In fact, tumor metastasis can occur in a still small "early" state of the primary tumor. More and more evidence shows that: in the state where the primary tumor is still microscopic, distant dissemination of tumor cells has already occurred. Therefore, inhibition of tumor metastasis is equally important as inhibition of tumor growth and should be performed early. To date, over 200 more anticancer drugs have been approved by the FDA, but few drugs that are effective in blocking tumor metastasis. At the same time, more and more studies have shown that tumor cells are mostly exposed to low concentrations of chemotherapeutic drugs, which often induce migration and invasion of tumor cells, and eventually often lead to metastasis and death of the patient.
Disclosure of Invention
The invention aims to provide an application of a natural product monomer in preparing anti-tumor metastasis medicaments, the natural product monomer is a compound shown in a formula I, and the compound containing the structure of the compound shown in the formula I can inhibit metastasis of tumor cells in different modes, remarkably influence the recombination of skeleton protein and inhibit lymph node metastasis, and improve the inhibition effect on various tumor cells.
In order to achieve the purpose, the invention adopts the following technical scheme:
the application of a natural product monomer in preparing an anti-tumor metastasis medicament is disclosed, wherein the natural product monomer is a compound shown in a formula I:
wherein:
r1 is selected from-H,
Or
R2 is selected from-H, -OH;
r3 is selected from-H, -OH;
r4 is selected from-H, -CH3, -CH2-OH, or-CH ═ O;
r5 is selected from-H, -OH;
r6 is selected from-H, -OH;
r7 is selected from-H, -OH or
R is glucoside.
Further, R comprises
Further, the compound of formula i is selected from one of the following compounds:
further, the compounds of formula I are useful for inhibiting the metastasis or/and proliferation of tumor cells.
Further, the dosage form of the compound of formula I is in the form of an orally administered formulation.
Further, the orally administered formulation may be in the form of tablets, which may contain fillers, adsorbents, binders, lubricants, dispersants, wetting agents, disintegrants, flavors, or colors, fillers such as starch, dextrin, binders and lubricants such as distilled water, ethanol, and disintegrants such as sodium carboxymethyl starch. Formulations for oral administration may be presented as hard or soft capsules, the active ingredient being mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules, the active ingredient being mixed with water or an oil, for example liquid paraffin or olive oil. The preparation form for oral administration can also be sustained-release tablets, controlled-release tablets, troches, dripping pills, micro-pills, aqueous or oily suspensions, emulsions, dispersible powders or granules, oral liquids, syrups or elixirs.
Further, the compound of formula I is in the form of a preparation for injection administration.
Further, the formulation for injection administration is in the form of: sterile aqueous or oily solutions, sterile powders, liposomes, emulsions, microemulsions, nanoemulsions or microcapsules. Sterile aqueous or oily solutions such as solutions in 1, 3-butanediol.
Cancer metastasis, the leading cause of death in cancer patients, is a multifactorial, multistep, concerted evolutionary process, influenced by the tumor microenvironment and numerous cytokines. The invention takes a compound DR-00345 and a compound DR-00992 as representatives, and researches whether the compound containing the structure of the compound shown in the formula I has the effect of inhibiting tumor metastasis on tumor cells.
The tumor cells with metastatic property must be recombined with the skeleton protein when the cells migrate so as to realize the spatial metastasis of the tumor cells. In the invention, through two groups of experiments of determining the influence of a medicament on the cell migration capacity by a cell scratch experiment and determining the influence of the medicament on the cell invasion capacity by a Transwell invasion experiment, the compound DR-00345 containing the structure of the compound shown in the formula I can inhibit the growth and proliferation of nasopharyngeal carcinoma cells S18, breast cancer cells MDA-MB-231 and gastric cancer SGC-7901, and obviously inhibit the migration and invasion of the nasopharyngeal carcinoma cells S18, the nasopharyngeal carcinoma cells 5-8F, the breast cancer cells MDA-MB-231, small cell lung cancer SBC3, non-small cell lung cancer H1299, gastric cancer MKN45, gastric cancer SGC 7901, gastric cancer MGC803 and pancreatic cancer PANC-1.
Furthermore, the compound DR-00992 containing the compound structure shown in the formula I can inhibit the growth capability of nasopharyngeal carcinoma cells S18-1A8 in vivo, and has a remarkable inhibition effect on lymph node metastasis.
Compared with the prior art, the invention has the following beneficial effects:
(1) the compound containing the structure of the compound shown in the formula I can inhibit the metastasis and proliferation of various tumor cells, and has a remarkable inhibiting effect on nasopharyngeal carcinoma cells S18, nasopharyngeal carcinoma cells 5-8F, breast cancer cells MDA-MB-231, small cell lung cancer SBC3, non-small cell lung cancer H1299, gastric cancer MKN45, gastric cancer SGC-7901, gastric cancer MGC803 and pancreatic cancer PANC-1.
(2) The compound containing the structure of the compound shown in the formula I can inhibit the metastasis of tumor cells in different modes, and obviously inhibit the lymph node metastasis, so that the inhibition effect on the tumor cells is improved.
Drawings
FIG. 1 is a chemical structural formula of a compound of formula I.
FIG. 2 shows the effect of compound DR-00345 on the growth of different tumor cells.
FIG. 3 is a cell scratch assay for compound DR-00345.
FIG. 4 is a graph showing the inhibitory effect of compound DR-00345 on the in vitro migration of different tumor cells.
FIG. 5 is a Transwell invasion assay of Compound DR-00345.
FIG. 6 shows the inhibitory effect of compound DR-00345 on the invasion of different tumor cells in vitro.
FIG. 7 is a photograph of a pharmacodynamic study of subcutaneous tumorigenic mice after administration of compound DR-00992.
FIG. 8 is a photograph of a pharmacodynamic study of subcutaneous tumorigenic mice orthotopic tumors after administration of compound DR-00992.
FIG. 9 is a graph of body weight change in subcutaneous tumorigenic mice after administration of compound DR-00992.
FIG. 10 is a graph of the change in tumor volume in subcutaneous tumor-forming mice after administration of compound DR-00992.
FIG. 11 is a graph showing the change in the number of metastases in mice with plantar lymph node metastases after administration of compound DR-00992.
FIG. 12 is a graph of body weight changes in mice with plantar lymph node metastases after administration of compound DR-00992.
FIG. 13 is a graph showing the change in tumor volume in mice with plantar lymph node metastasis following administration of compound DR-00992.
FIG. 14 is a photograph of a pharmacodynamic study of plantar lymph node metastatic mice after compound DR-00992 administration.
In the figure, inhibition rate is inhibition rate, concentration is concentration, Negative is Negative Control, Positive is Positive Control, Relative percent of scratch closure, Relative percent of affected cells is Relative percent of affected cells, body weight is body weight, Days is Days, tumor volume is tumor volume, Control is model Control, Number of mice is Number, Metastasis is Metastasis, Non-Metastasis is Non-Metastasis, and tumor weight is tumor weight.
Detailed Description
The present invention will be described in further detail with reference to the following examples. It should not be understood that the scope of the above-described subject matter of the present invention is limited to the following examples.
Example 1 MTT assay of the Effect of drugs on cell growth
1.1 subjects: nasopharyngeal carcinoma cells S18; breast cancer cells MDA-MB-231; gastric cancer SGC-7901.
1.2 Experimental drugs: compound DR-00345.
1.3 Experimental methods: plate paving: cells in log phase were collected, cell suspension concentration was adjusted, 90ul was added to each well, and plating was performed to achieve a cell density of 10000 per well. Adding medicine: 5% CO2, incubated at 37 ℃ until the cell monolayer has spread to the bottom of the well (96 well flat bottom plate), and the drug is added in a concentration gradient. 5% CO2, incubated at 37 ℃ for 72 hours and observed under an inverted microscope. 20ul of MTT solution (5mg/ml, i.e.0.5% MTT) was added to each well and incubation was continued for 4 h. The culture was terminated and the culture medium in the wells was carefully aspirated. 150ul of dimethyl sulfoxide was added to each well, and the mixture was shaken on a shaker at a low speed for 10min to dissolve the crystals sufficiently. The absorbance of each well was measured at the ELISA OD490nm to calculate the relative viability of the cells. In the experiment, a culture medium without cells is used as a blank control, and 20ul of MTT solution is added into each well to be used as an experiment control group and an experiment group containing samples.
1.4 relative survival rate ═ 100% (experimental OD-blank OD)/(control OD-blank OD) ×
The results show that: as can be seen from FIG. 1, compound DR-00345 was able to inhibit the growth and proliferation of nasopharyngeal carcinoma cells S18 concentration-and time-dependently, with an IC50 of 0.276. mu.M. And the effect on cell growth of breast cancer cells MDA-MB-231 and gastric cancer SGC-7901 was tested, while the IC50 of breast cancer cells MDA-MB-231 and gastric cancer SGC-7901 was 3.831. mu.M and 0.1637. mu.M, respectively. Compared with three cancer cells IC50, the compound DR-00345 has obvious effect of inhibiting gastric cancer cell SGC-7901.
Example 2 cell scratch assay to determine the Effect of drugs on cell migration Capacity
2.1 subjects: nasopharyngeal carcinoma cells S18; nasopharyngeal carcinoma cells 5-8F; breast cancer cells MDA-MB-231; small cell lung cancer SBC 3; non-small cell lung cancer H1299; gastric cancer MKN 45; gastric cancer SGC-7901; MGC803 for gastric cancer; pancreatic cancer PANC-1.
2.2 Experimental drugs: compound DR-00345.
2.3 Experimental methods: a marker pen is used for fine heads at the back of a 6-hole plate, the fine heads are matched with a ruler, lines are uniformly drawn, the lines penetrate through holes approximately every 0.5-1cm, and generally three lines are drawn and are sequentially named as lines a, b and c. The line b crosses the midpoint, and the other two lines are equally spaced on both sides. Six-well plate, each with 2ml, different cell plate concentration, such as S18, each with 5X 105 cells, each with 2 multiple wells, for about 24h culture. The cell number is preferably 70-80% of the cell number after the cell is adhered to the wall overnight, and the cell number is properly adjusted. Opening the cover of the orifice plate, sucking off the old culture medium, putting a ruler vertical to the b-line frame on the orifice plate, using 200ul of gun head to cling to the ruler to move uniformly to manufacture a cell scribing line, and likewise, scribing two parallel lines at equal intervals on two sides of the line, which are respectively named as a line 1 and a line 2. The cells were washed 3 times with sterile 1 × PBS, and after the scraped cells were removed, serum medium was added and placed in a 37 ℃ 5% CO2 incubator. Samples were taken at 0, 24 hours and photographed.
The results show that: cell migration is the basic step of tumor cell metastasis, and it can be seen through cell scratch test whether compound DR-00345 can inhibit the migration of cancer cells. As can be seen from figures 2 and 3, after 24 hours of action, the compound DR-00345 has significant effects on most cancer cells, particularly has significant inhibitory effects on nasopharyngeal carcinoma cells 5-8F, breast cancer cells MDA-MB-231, non-small cell lung cancer H1299, gastric cancer SGC-7901, gastric cancer MGC803 and pancreatic cancer PANC-1.
Example 3 Transwell invasion assay to determine the effect of drugs on the ability of cells to invade
3.1 subjects: nasopharyngeal carcinoma cells S18; nasopharyngeal carcinoma cells 5-8F; breast cancer cells MDA-MB-231; small cell lung cancer SBC 3; non-small cell lung cancer H1299; gastric cancer MKN 45; gastric cancer SGC-7901; MGC803 for gastric cancer; pancreatic cancer PANC-1.
3.2 Experimental drugs: compound DR-00345.
3.3 Experimental methods: coating of basement Membrane (4 ℃ procedure) Matrigel (10mg/ml to 250. mu.g/ml) was diluted with serum-free cell culture medium DMEM at 4 ℃. When in use, 50. mu.l of Matrigel was added to 1950. mu.l of DMEM in an EP tube. 100 μ l of the diluted gel was slowly added dropwise to the upper chamber of a 24-well transwell and incubated in an incubator for 1 hour. Preparing a cell suspension; digesting the cells, centrifuging after terminating digestion, discarding the culture solution, washing with PBS for 1 time, resuspending in a serum-free culture medium, and adjusting the cell density to a proper concentration. Inoculating cells; 200. mu.l of the cell suspension was added to the upper chamber of a Transwell and 2. mu.l of 10% BSA was added. Immediately below the 24-well plate, 800. mu.l of medium containing 10% FBS was typically added. And culturing for 24h conventionally. Staining cells; the Transwell chamber was removed, the medium in the well was discarded, the cells in the upper chamber were wiped off with a cotton swab and placed in a clean 24-well plate. Wash 1 time with calcium-free 1 × PBS, fix with methanol for 30 min, and air dry the chamber in a fume hood. 0.1% crystal violet stain for 20min, gently wipe off the upper non-migrated cells with a cotton swab, wash 1 time with PBS. The results were counted, observed under a 5X microscope, and cells were observed under a 10X microscope at random in five visual fields.
The results show that: as can be seen from FIGS. 4 and 5, it is possible to influence the invasion abilities of nasopharyngeal carcinoma cells S18, nasopharyngeal carcinoma cells 5-8F, breast cancer cells MDA-MB-231, small cell lung cancer SBC3, non-small cell lung cancer H1299, gastric cancer MKN45, gastric cancer SGC-7901, gastric cancer MGC803 and pancreatic cancer PANC-1 to influence the development and development of the above cancer cells.
Example 4 subcutaneous tumor formation experiment
4.1 subjects: nasopharyngeal carcinoma cell S18-1A 8.
4.2 Experimental drugs: compound DR-00992.
4.3 Experimental methods: preparing tumor cells; collecting nasopharyngeal carcinoma cells S18-1A8 with good growth state in logarithmic growth phase, digesting, counting, diluting with 1 × PBS to 1.5 × 107one/mL (75% alcohol sterilized mice axilla in the medial lateral subcutaneous area). 100 μ L of cells were suspended, i.e., 1.5X 106The individual cells were injected subcutaneously into the right axilla, medial lateral to the right. After 7-10 days of general inoculation, the tumor can be seen to grow up and the tumor body is ready for growingRandomly grouping experiments according to the first index tumor size and the second index mouse weight when the diameter is about 5-8 mm, and dividing the experiments into a solvent group (Control) and a low dose group [ DR-00992(2mg/kg)]And high dose group [ DR-00992(5mg/kg)](ii) a Tumor volume and animal body weight were measured 8 days after injection of tumor cells every 2-3 days. Measuring the long diameter L and the short diameter W of the tumor by a vernier caliper regularly according to the formula V ═ L multiplied by W2X 0.52, tumor size was calculated and growth curves were plotted. When the diameter is about 5-8 mm, the injection is carried out in the abdominal cavity, 2 mg/kg/day is injected in the low-dose group, 5 mg/kg/day is injected in the high-dose group, the solvent group is injected with the solvent solution with the same volume, and after the continuous administration is carried out for 14 days, subcutaneous in-situ tumor is extracted.
The results show that: as can be seen from FIGS. 6 to 9, the growth state of the mice was continuously observed in the experiment, the nasopharyngeal carcinoma cells of the mice in the solvent group grew into large tumor masses, and the nasopharyngeal carcinoma cells in the low-dose group and the high-dose group were significantly reduced in size, even were unable to form tumors. Further, the result of extracting subcutaneous in situ tumor also shows that the compound DR-00992 can obviously inhibit the growth ability of nasopharyngeal carcinoma cells in vivo.
Example 5 plantar lymph node metastasis test
5.1 subjects: nasopharyngeal carcinoma cell S18-1A 8.
5.2 Experimental drugs: compound DR-00992.
5.3 Experimental methods: nude mouse ordering: female BALB/c nude mice of 3-4 weeks of age were ordered from the Guangdong provincial medical laboratory animal center and kept in an SPF rearing room for 5 days while isolated observation was made. Mice were randomly grouped by weight. Cell inoculation: collecting nasopharyngeal carcinoma cells S18-1A8 with good growth state in logarithmic growth phase, digesting, counting, diluting with 1 × PBS to 5 × 106pieces/mL (75% alcohol sterilized mouse footpad). 20 μ L of cells were suspended, i.e., 1X 105 cells were injected into the left posterior sole of nude mice. The normal control group was injected into the left rear sole of nude mice with 20. mu.L of 1 XPBS. One week after cell injection, 1% sodium pentobarbital was anesthetized by intraperitoneal injection (20ul/140g), and D-fluorescein (potassium salt) was injected intraperitoneally at a concentration of 15mg/ml and 5 ul/g. Luciferase signals were then detected using a BioRadChemdoc XP chemiluminescence apparatus to confirm successful tumor implantation. Each mouse was administered sequentially according to the dosing schedule100 μ l was administered by intraperitoneal injection on day 42. Weighing the primary tumor: the left and right hind limbs of the nude mice were each cut, and the weight of the left hind limb minus the weight of the right hind limb was used as the weight of the primary tumor. Lymph node RNA, in situ tumor RNA and protein were extracted using Trizol method. And (3) RNA quality detection, including purity detection and electrophoresis detection. Reverse transcription and Real-time PCR: taking 1 mu g of RNA for reverse transcription, taking 10 mu g of cDNA equivalent of RNA for Real-time PCR detection, and detecting the expression quantity of the Luciferase gene. The Ct value was 32 as the detection threshold.
The results show that: lymph node metastasis is one of the common pathways for tumor metastasis. As can be seen from FIGS. 10 to 13, the color development range in the control is large, and lymph nodes have metastasis; the color development range of compound DR-00992(0.4mg/kg) was reduced, lymph node metastasis was less pronounced, and when the concentration of compound DR-00992 was increased, the color development range of compound DR-00992(2mg/kg) was smaller. As can be seen, compound DR-00992 has significant inhibitory effect on plantar lymph node metastasis.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (7)
1. The application of a natural product monomer in preparing an anti-tumor metastasis medicament is characterized in that the natural product monomer is a compound shown in a formula I:
wherein:
r1 is selected from-H,
R2 is selected from-H, -OH;
r3 is selected from-H, -OH;
r4 is selected from-H, -CH3, -CH2-OH, or-CH ═ O;
r5 is selected from-H, -OH;
r6 is selected from-H, -OH;
r7 is selected from-H, -OH or
R is glucoside.
2. The use of the natural product monomers of claim 1 in the preparation of a medicament for inhibiting tumor metastasis, wherein the compound of formula i is selected from one of the following compounds:
3. the use of a natural product monomer as claimed in claim 1 or 2 in the manufacture of a medicament for the inhibition of tumor metastasis, wherein the compound of formula i is used to inhibit metastasis or/and proliferation of tumor cells.
4. The use of natural product monomers in the preparation of a medicament for the treatment of tumor metastasis as claimed in claim 3, wherein the compound of formula I is in the form of an orally administered formulation.
5. The use of the natural product monomers of claim 4 in the preparation of a medicament for inhibiting tumor metastasis, wherein said oral administration is in the form of: tablets, hard or soft capsules, sustained-release tablets, controlled-release tablets, troches, dripping pills, pellets, aqueous or oily suspensions, emulsions, dispersible powders or granules, oral liquids, syrups or elixirs.
6. The use of the natural product monomers of claim 3 in the preparation of a medicament for inhibiting tumor metastasis, wherein the compound of formula i is in the form of an injectable formulation.
7. The use of the natural product monomer of claim 6 in the preparation of a medicament for inhibiting tumor metastasis, wherein said injectable formulation is in the form of: sterile aqueous or oily solutions, sterile powders, liposomes, emulsions, microemulsions, nanoemulsions or microcapsules.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911262554.8A CN110882267A (en) | 2019-12-11 | 2019-12-11 | Application of natural product monomer in preparation of anti-tumor metastasis drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911262554.8A CN110882267A (en) | 2019-12-11 | 2019-12-11 | Application of natural product monomer in preparation of anti-tumor metastasis drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110882267A true CN110882267A (en) | 2020-03-17 |
Family
ID=69751396
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911262554.8A Pending CN110882267A (en) | 2019-12-11 | 2019-12-11 | Application of natural product monomer in preparation of anti-tumor metastasis drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110882267A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113952295A (en) * | 2021-11-10 | 2022-01-21 | 广州市朝利良生物科技有限公司 | Anti-tumor metastasis medicine and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040082521A1 (en) * | 2002-03-29 | 2004-04-29 | Azaya Therapeutics Inc. | Novel formulations of digitalis glycosides for treating cell-proliferative and other diseases |
| WO2004087121A2 (en) * | 2003-03-28 | 2004-10-14 | Azaya Therapeutics, Inc. | Water soluble formulations of digitalis glycosides for treating cell-proliferative and other diseases |
| CN102219821A (en) * | 2011-05-05 | 2011-10-19 | 沈阳药科大学 | Cardiac glycoside compounds and antitumor application thereof |
-
2019
- 2019-12-11 CN CN201911262554.8A patent/CN110882267A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040082521A1 (en) * | 2002-03-29 | 2004-04-29 | Azaya Therapeutics Inc. | Novel formulations of digitalis glycosides for treating cell-proliferative and other diseases |
| WO2004087121A2 (en) * | 2003-03-28 | 2004-10-14 | Azaya Therapeutics, Inc. | Water soluble formulations of digitalis glycosides for treating cell-proliferative and other diseases |
| CN102219821A (en) * | 2011-05-05 | 2011-10-19 | 沈阳药科大学 | Cardiac glycoside compounds and antitumor application thereof |
Non-Patent Citations (3)
| Title |
|---|
| BETTE S. POLLARD等: "Digitoxin Inhibits Epithelial-to-Mesenchymal-Transition in Hereditary Castration Resistant Prostate Cancer", 《FRONTIERS IN ONCOLOGY》 * |
| 无: "bovoside A", 《SPECTROSCOPIC DATA OF STEROID GLYCOSIDES: SPIROSTANES, BUFANOLIDES, CARDENOLIDES》 * |
| 杨秀伟: "《中药成分的吸收、分布、代谢、排泄、毒性与药效 上册》", 31 August 2006, 中国医药科技出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113952295A (en) * | 2021-11-10 | 2022-01-21 | 广州市朝利良生物科技有限公司 | Anti-tumor metastasis medicine and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2020103364A4 (en) | Ositinib-resistant cell line NCI-H1975/AR and application thereof | |
| CN110882267A (en) | Application of natural product monomer in preparation of anti-tumor metastasis drugs | |
| CN109700799A (en) | Antrocin and its micro-nano granules are preparing the application in immunotherapy of tumors drug | |
| AU2020103247A4 (en) | Third-generation EGFR-TKI drug-resistant cell strain and application thereof | |
| CN103860542A (en) | Application of cycloicaritin in preparation of anti-tumor composition | |
| CN113143913A (en) | Application of eudesmane type sesquiterpene compound in preparation of anti-pancreatic cancer drugs | |
| CN109200041B (en) | Application of cyperus azulene ketone in preparing medicine for treating esophageal squamous cell carcinoma by inhibiting SIRT1 gene expression | |
| CN108653281B (en) | Application of E-2-styryl benzimidazole compound in preparation of anti-hepatitis B virus drugs | |
| CN114195779A (en) | Synthesis method of 9-0-ethyl ether berberberrubine and application thereof in preparation of antitumor drugs | |
| CN113995753A (en) | Application of Chinese medicinal molecular sophocarpine in preparing medicament for treating glioblastoma | |
| US9138422B2 (en) | Method of using antimycin A to downregulate Wnt/b-catenin pathway to treat gefitinib resistant cancer | |
| CN113384593A (en) | Application of saikosaponin A in preparing medicine for inhibiting angiogenesis | |
| CN107260752B (en) | Synergistic anti-pancreatic cancer pharmaceutical composition | |
| CN111773220A (en) | New medicinal application of apatinib or pharmaceutically acceptable salts thereof | |
| CN113952350B (en) | Application of dihydroartemisinin and gypenoside-L in preparation of antitumor drugs | |
| CN109568327A (en) | Doxycycline application in preparation of anti-tumor drugs | |
| CN116267797A (en) | Lactic acid preparation capable of promoting tumor growth, preparation method and application thereof | |
| CN111281870B (en) | Medicine for inhibiting invasion and metastasis of oral cancer cells | |
| CN101664401A (en) | Application of usnic acid in preparation of drugs inhibiting angiogenesis | |
| SE437931B (en) | PHARMACEUTICAL COMPOSITION WITH ANTITUMOR EFFECTS CONTAINING PHOSPHATE OF POLYHEXAMETHYLENGUANIDINE WITH THE FORMULA | |
| CN117327797B (en) | Application of RRP1 gene in treating non-small cell lung cancer | |
| CN109303779B (en) | Application of aminopyridine imidazolone derivatives in preparation of antitumor drugs | |
| CN111407767B (en) | Application of sulfamonomethoxine derivative in preparation of antitumor drugs | |
| CN116370462A (en) | New pharmaceutical application of anti-artemia carbazole amino alcohol compound | |
| CN113908148B (en) | Application of nobiletin in preparation of anti-cholangiocarcinoma drugs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200317 |