CN116808051A - Application of gamabufotalin in preparation of medicines for treating platinum-resistant ovarian cancer - Google Patents
Application of gamabufotalin in preparation of medicines for treating platinum-resistant ovarian cancer Download PDFInfo
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 title claims abstract description 122
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- 239000003814 drug Substances 0.000 title claims abstract description 54
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Pharmacology & Pharmacy (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
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Abstract
The invention discloses an application of gamabufotalin in preparing a medicament for treating platinum-resistant ovarian cancer, and belongs to the technical field of cancer medicaments. The embodiment of the invention proves the application of the gamabufotalin in preparing the medicines for treating the platinum-resistant ovarian cancer. The dosage of the gamabufotalin is 0 mg/kg-20 mg/kg. The embodiment of the invention demonstrates the inhibition effect of the gamabufotalin CS-6 on the proliferation of human platinum-resistant ovarian cancer cells, and the treatment effect of the gamabufotalin CS-6 on a human platinum-resistant ovarian cancer animal model. The gamabufotalin CS-6 (0 mg/kg-20 mg/kg) can obviously reduce the volume and weight of human platinum drug-resistant ovarian cancer tumors after being dosed, has obvious effect of inhibiting platinum drug-resistant ovarian cancer tumors, can be applied to preparation of a platinum drug-resistant ovarian cancer treatment drug, is applied to treatment of human platinum drug-resistant ovarian cancer, exploits a new application of gamabufotalin, and provides a choice for expanding a novel platinum drug-resistant ovarian cancer treatment drug.
Description
Technical Field
The invention belongs to the technical field of cancer medicaments, and particularly relates to application of gamabufotalin in preparing a medicament for treating platinum-resistant ovarian cancer.
Background
Ovarian cancer refers to malignant diseases occurring in the ovaries, and the clinical characteristics and treatment patterns of malignant tumors originating in the fallopian tubes and peritoneum are similar to those of ovarian cancers, and are often also commonly called ovarian cancer. Ovarian cancer is of various histological types, mainly of epithelial origin. Ovarian cancer can occur at any age and the age of onset of tumors of different histological types, such as germ cell tumors most commonly found in women under 20 years of age, borderline tumors in women between 30 and 40 years of age, and in general ovarian cancer occurs mostly in women over 50 years of age. In China, the incidence rate of ovarian cancer is 3 rd in gynecological tumors, and the incidence rate of ovarian cancer accounts for about 23% of all female reproductive system tumors, and the tendency is that the incidence rate of ovarian cancer rises year by year. The patients dying from ovarian cancer every year in China are about 2.5 ten thousand, and occupy the first of gynecological malignant tumors. Early lesions of ovarian cancer are often asymptomatic, difficult to find, and symptoms of late lesions are atypical. Ovarian cancer is prone to metastasis and recurrence, and factors that affect patient recurrence are diverse, including: stage of tumor, histological type, size of residual lesion after surgery, chemotherapy regimen, age, general physical condition, etc. The overall prognosis of ovarian cancer is poor, and mainly depends on comprehensive treatment such as combined radiotherapy, chemotherapy, targeted treatment and the like after operation.
The first-line treatment scheme for the epithelial ovarian cancer clinically is a treatment scheme combining platinum and yew, the first-line treatment is almost 20 years at present, and no other high-level evidence-based medical evidence exists at present, so that the first-line chemotherapy scheme can be driven to take effect. Often, congenital resistance is less common in ovarian cancer patients, most of which begin to develop chemotherapy resistance after undergoing multiple chemotherapies. The NCCN guideline always uses the core drug platinum in the chemotherapy scheme as a mark for distinguishing the drug resistance property, so that whether the drug is sensitive to the platinum is a key node for judging whether an ovarian cancer patient has a recommended treatment scheme or not, and the method is a hot spot of current research.
The platinum resistance and the sensitive recurrence of the ovarian cancer have obvious differences in the aspects of symptoms, etiology and treatment scheme selection, and are essentially due to obvious changes in tumor cell characteristics and biological behaviors after the platinum resistance of the ovarian cancer. When the platinum resistance of the ovarian cancer occurs, the treatment effect is far lower than the platinum sensitive period no matter the chemotherapy drug is replaced, or the anti-angiogenesis targeting drug, the PARP inhibitor, the PD1 and the like are used. The sensitivity of platinum drugs not only represents the difference of the treatment response of ovarian cancer to platinum chemotherapeutics, but also represents the large difference of tumor immune states.
Platinum-resistant recurrent ovarian cancer patients, for whom surgical treatment is not recommended, will have shorter and shorter intervals of the recurrence cycle. And the second-line treatment uses platinum chemotherapy to be no longer effective, so the effective rate of the second-line treatment is less than 20 percent, and no one scheme can be used as a treatment standard scheme for platinum drug resistance recurrence of ovarian cancer at present. Therefore, for platinum-resistant patients, clinically, there is often no drug-free treatment.
Therefore, the task of searching for a more effective treatment method for platinum-resistant ovarian cancer and improving clinical efficacy is urgent.
The Bufonis venenum (CS) is dry secretion of postaural gland or skin gland of Bufomelanins (BufobalgargargarizansCantor) or Bufomelanins (Bufomelanos-ictus Schneider) of Bufoidae, and has effects of removing toxic substance, relieving swelling and pain. The traditional Chinese medicine is clinically used for anesthesia, sore, furuncle, carbuncle, swelling, heatstroke, vomiting and diarrhea, sore throat, toothache, cancer and the like. The main chemical components of the toad venom comprise bufogenin, indole alkaloids, sterols and other compounds, wherein the bufodienolide compound is a main antitumor active component in CS.
Xibufotalin (CS-6) is a major bufadienolide in CS, and CS-6 has more stable metabolic activity and fewer adverse effects than other CS bioactive toxins. The research on the action mechanism of CS-6 at home and abroad mainly comprises the steps of inhibiting the proliferation of tumor cells, promoting the apoptosis, reducing the drug resistance of anticancer drugs and the like. In the past researches and clinical applications, although partial bufonin preparations are used for treating leukemia, gastrointestinal tumors and the like, bufadienolide compounds are not used for treating platinum-resistant ovarian cancer.
Disclosure of Invention
The embodiment of the invention aims to provide application of the gamabufotalin in preparing a medicament for treating platinum-resistant ovarian cancer, and the embodiment of the invention shows that the gamabufotalin can be used for treating the platinum-resistant ovarian cancer and can be used for preparing an anti-tumor medicament for treating the platinum-resistant ovarian cancer.
The aim of the invention is achieved by the following technical scheme:
the invention aims to provide a novel application of the gamabufotalin in treating platinum-resistant ovarian cancer, and the inhibition of the gamabufotalin on the proliferation of platinum-resistant ovarian cancer cells is proved by in vivo experiments, and the inhibition of the gamabufotalin on the proliferation, invasion and metastasis of platinum-resistant ovarian cancer cells is proved by in vitro experiments, so that the gamabufotalin can be used for treating the platinum-resistant ovarian cancer.
The embodiment of the invention proves that the gamabufotalin can be used for preparing the anti-tumor medicine for treating platinum drug-resistant ovarian cancer.
The molecular formula of the gamabufotalin is as follows: c (C) 26 H 36 O 6 Molecular weight: 402.53, the structural formula is shown as formula I:
the application of the gamabufotalin in preparing medicaments for treating platinum-resistant ovarian cancer can be used for single administration or combined treatment.
The combined treatment comprises radiotherapy, chemotherapy and operation treatment.
The gamabufotalin can be any pharmaceutically acceptable dosage form.
The gamabufotalin can be in any pharmaceutically acceptable dose; preferably, the dose of the gamabufotalin is 20mg/kg.
Compared with the prior art, the invention has the following beneficial effects:
1. the examples of the present invention demonstrate the inhibition of proliferation of human platinum-resistant ovarian cancer cells by Xenopus for its CS-6.
2. The examples of the present invention demonstrate the therapeutic effect of gamabufotalin CS-6 on human platinum-resistant ovarian cancer animal models.
3. The embodiment of the invention can obviously reduce the volume and weight of human platinum drug-resistant ovarian cancer tumor after the administration of the gamabufotalin CS-6 (20 mg/kg), has obvious effect of inhibiting the platinum drug-resistant ovarian cancer tumor, can be applied to preparation of a platinum drug-resistant ovarian cancer treatment medicament, is applied to treatment of human platinum drug-resistant ovarian cancer, exploits a new application of gamabufotalin, and provides a choice for expanding a novel platinum drug-resistant ovarian cancer treatment medicament.
Drawings
FIG. 1 is a graph showing the results of inhibition of proliferation of Xenopharyngod against human ovarian cancer SKOV3, A2780 and cisplatin resistant strains SKOV3/DDP and A2780/DDP cells. Wherein the data are expressed as "mean inhibition of each concentration ± standard deviation of each effect".
FIG. 2 shows the soft agar colony rate of cisplatin-resistant ovarian cancer cells SKOV3/DDP after treatment with each dose group of gamabufotalin. Wherein data are expressed as "mean ± standard deviation"; comparison of significant differences in apoptosis rates between control and drug-treated groups using one-way anova (one-way anova) test with Dunnett' smulteplocrisonstest test, P values less than 0.05 were considered significant differences.
FIG. 3 is a graph showing the results of inhibition of cisplatin-resistant ovarian cancer cells SKOV3/DDP by Xenopus for the treatment of ovarian cancer. Wherein data are expressed as "mean ± standard deviation"; comparison of significant differences in apoptosis rates between control and drug-treated groups using one-way ANOVA (one-way ANOVA) test with Dunnett' smulteplocrisonstest test, P values less than 0.05 were considered significant differences.
FIG. 4 is a graph showing the growth of human cisplatin-resistant ovarian cancer cells SKOV3/DDP in each experimental group in a subcutaneous tumor model. Wherein data are expressed as "mean ± standard deviation"; comparing the relative tumor volume significance differences between control and treatment groups using the unpaired t-test (Welch' scan), P values less than 0.05 were considered significant differences.
FIG. 5 is a graph of the photographed results of tumors from each experimental group in the SKOV3/DDP subcutaneous implant tumor model after completion of administration.
FIG. 6 is a graph showing the tumor weight results of the day bufalin after completion of tumor administration by SKOV3/DDP transplantation in nude mice.
Wherein data are expressed as "mean ± standard deviation"; comparing the significant difference in tumor weights between the vehicle control group and the gamabufotalin-dosed group with a unpaired t-test (Welch' scan), P-values less than 0.05 were considered significant differences.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
At present, the treatment of platinum drug-resistant ovarian cancer lacks effective treatment of natural product drugs, and in order to solve the technical problems, the invention provides application of gamabufotalin in preparing drugs for treating platinum drug-resistant ovarian cancer.
The experimental materials used in the following examples are as follows: cell lines of human ovarian cancer cell lines SKOV3, A2780 and cisplatin resistant strains SKOV3/DDP and A2780/DDP are provided by the life technology Co., ltd; 96-well plates were purchased from Costar (catalog number: 3599); RPMI1640 medium was purchased from Gibco corporation (catalog number: C11995500 BT); fetal bovine serum was purchased from Gibco corporation (catalog number 10270-106); CCK-8 kit was purchased from Menlan organism (catalog number: MA 0218); dimethyl sulfoxide (DMSO) and cisplatin were purchased from beijing solibao technologies limited; the gamabufotalin (CS-6) is purchased from Nanjing spring and autumn bioengineering limited company, and has HPLC purity of more than 98%, and is stored at-20deg.C in a sealed manner.
The experimental apparatus used in the following examples is as follows:
experimental instrument: ultra clean bench (Suzhou purification model BHC-1000IIA 2), CO2 incubator (Thermo model 3111), microplate reader (Thermo MultiscanMK 3).
Embodiment one: effect of Xiubufalin on proliferation of human platinum-resistant ovarian cancer cells
Test article: 2mg of the solution was weighed, and 2.5 mM of LDMSO was added for dissolution to prepare a 2mM/L solution.
The treatment method comprises the following steps: the proliferation inhibition effect of the gamabufotalin on human platinum-resistant ovarian cancer cells was evaluated by using the CCK-8 method: human ovarian cancer SKOV3, A2780 and cisplatin resistant strains SKOV3/DDP and A2780/DDP cells were digested with pancreatin, counted and mixed with whole culture broth (10% fetal bovine serum+90% RPM 1640 medium) to prepare a cell suspension with a concentration of 2X 104 cells/mL. mu.L of cell suspension (2X 103 cells per well) was added to each well of the 96-well plate, followed by culturing in a 5% CO2 incubator at 37℃for 16 hours; diluting the drug with complete culture medium to different gradient concentrations (CS-6:1.95 nM/L-2000nM/L; cisplatin: 0.0195 mu M/L-20 mu M/L), adding 100 mu L of corresponding drug-containing culture medium into each well, setting up a solvent (DMSO) control group and a cell-free culture solution control, placing a 96-well plate at 37 ℃ for 5% CO2, culturing in a culture box for 72 hours, adding 10 mu L of CCK-8 solution into each well, continuing culturing for 2 hours, detecting the absorbance of each well, namely the OD value, by using an enzyme-labeling instrument at the wavelength of lambda=450 nM, subtracting the OD value of the cell-free culture solution average value from the average value of each multiplexing well as the OD value of the group of cells, and comparing the OD value of the cell-free culture solution average value with the solvent control, and calculating the cell survival rate after drug treatment.
As a result, as shown in FIG. 1, the ovarian cancer cisplatin-resistant strains (SKOV 3/DDP and A2780/DDP) were more resistant to cisplatin than the parental cell lines (SKOV 3 and A2780), at half-inhibitory concentrations (IC 50 ) The method comprises the following steps of: a2780 (0.14. Mu.M/L), A2780/DDP (2.55. Mu.M/L), SKOV3 (0.36. Mu.M/L) and SKOV3/DDP (7.66. Mu.M/L). The gamabufotalin has obvious proliferation inhibition effect on human ovarian cancer SKOV3, A2780 and cisplatin resistant strains SKOV3/DDP and A2780/DDP cells, and IC thereof 50 Are each less than 50nM/L,17.88nM/L, 26.98nM/L, 27.73nM/L, and 25.27nM/L.
Embodiment two: soft agar colony formation inhibition effect of gamabufotalin on human cisplatin-resistant ovarian cancer cells SKOV3/DDP
Test article: the gamabufotalin solution is prepared by the method described in example one.
The treatment method comprises the following steps: completely solubilized 5% agar and pre-warmed complete medium (10% fetal bovine serum+90% rpm 1640 medium) were mixed at 1:9 proportion is evenly mixed and added into a 6-hole cell culture plate, each hole contains 2mL of 0.5% agar culture medium, and agar is completely solidified at room temperature. Human cisplatin-resistant ovarian cancer cells SKOV3/DDP were digested with pancreatin, counted, and mixed with complete culture medium to give a cell suspension at a concentration of 1X 103 cells/mL, and vehicle DMSO control, cisplatin-treated group (0.2. Mu.M/L) and Xenopyrafen-treated group (20 nM/L) were provided, each group having 4 parallel wells. 1mL of the cell suspension preheated at 37 ℃ is transferred into a centrifuge tube, 50 mu L of 5% agar is added into the centrifuge tube, and the mixture is uniformly mixed with the same volume, thus obtaining the 0.24% semisolid agar culture medium. The prepared semi-solid agar medium was immediately added to the petri dish with the underlying agar, and the agar solidified at room temperature. The culture was allowed to stand at 37℃for 10 days with 5% CO 2. The number of cell colonies counted under the microscope is greater than 50, and then the colony formation rate is calculated as follows: colony formation rate (%) = (colony number/1000) ×100.
The results are shown in fig. 2, and the results of the soft agar colony formation experiments show that cisplatin has no significant effect on soft agar colony formation of SKOV3/DDP cells (p= 0.7065). Soft agar colony formation of SKOV3/DDP cells in the daily bufotalin (20 nM/L) treated group was significantly lower than that in the vehicle (DMSO) control group (CS-6 vs. vehicle, P < 0.0001).
Embodiment III: test article for inhibiting invasion of bufotalin on cisplatin-resistant ovarian cancer cells SKOV 3/DDP: the gamabufotalin solution is prepared by the method described in example one.
The treatment method comprises the following steps: human cisplatin-resistant ovarian cancer cells SKOV3/DDP were digested with pancreatin, counted, and mixed with RPMI-1640 medium to prepare a cell suspension at a concentration of 1X 105 cells/mL. 600 μl of complete medium was added to the 24-well plate transwell lower chamber, and vehicle DMSO control, cisplatin-treated group (0.2 μM/L) and Xenopharynx-treated group (20 nM/L) were set, with 4 parallel wells each. The Transwell chamber was placed in a 24-well plate with forceps, 100. Mu.L of the cell suspension was taken into the Transwell upper chamber of the pre-coated Matrigel, and placed into an incubator for cultivation for 24 hours. The chamber was removed, the medium was aspirated, and the Matrigel and cells in the upper chamber were gently rubbed off with a cotton swab. Adding 600 μl of 4% paraformaldehyde into a new 24-well plate, fixing the chamber for 20-30 min, discarding the fixing solution, dyeing with 0.1% crystal violet dye solution for 10 min, washing with deionized water for 3 times, air drying, and photographing under high power microscope. After staining, 600. Mu.L of 33% acetic acid was added to each Transwell chamber, crystal violet was completely eluted, and after sufficient shaking, 100. Mu.L of the eluate was taken and the absorbance at 570nm (OD 570) was measured by an ELISA reader.
The results are shown in fig. 3, and the Transwell cell invasion experimental results show that compared with the vehicle (DMSO) control group, cisplatin has no significant effect on the cell invasion of SKOV3/DDP cells (p= 0.2803); the Xenopus tabacum (20 nM/L) treated group significantly inhibited the invasive capacity of SKOV3/DDP cells (CS-6 vs. vehicle, P < 0.0001).
Embodiment four: efficacy experiment of nude mice subcutaneously transplanted with cisplatin-resistant ovarian cancer cells SKOV3/DDP tumor model
Experimental animals: BALB/c nude mice, females, 4 weeks old, weighing approximately 17g, purchased from Hunan Stokes Lemonda laboratory animal Co., ltd., production license number: SCXK (xiang) 2019-0004, animal eligibility number: 430727221102297442. feeding environment: SPF stage.
The experimental animals are all fed in an independent ventilation box with constant temperature and humidity, the temperature of a feeding room is 20-26 ℃, the humidity is 40-70%, ventilation is performed for 10-20 times per hour, and the light and shade alternation time is 12h/12h; the cobalt 60 radiation sterilized mouse complete pellet feed is continuously supplied, the mouse complete pellet feed is not limited to be taken freely, tap water is drunk (the mouse complete pellet feed is used after high-pressure steam sterilization), and a drinking bottle is supplied with water uninterruptedly and is taken freely. The feeding rat box is a polysulfone rat box, and is used after autoclaving, and the specification is 325mm multiplied by 210mm multiplied by 180mm; the padding is autoclaved corncob, 5 animals per box; and marking the experimental animal by marking an ear tag.
Experimental materials: the gamabufotalin is purchased from Nanjing spring and autumn bioengineering limited company, has HPLC purity of more than 98%, and is stored at-20deg.C in a sealed manner. PEG300 was purchased from the sea Ann petrochemical plant in Jiangsu province; PBS was purchased from the division of biosciences, the division of the western sciences, the division of the western world, the division of the yama; DMSO was purchased from beijing solibao technologies limited.
Preparing the medicine: the Xenopus tabacum powder was weighed and dissolved in vehicle solution (10% DMSO+30% PEG300+60% PBS).
The experimental method comprises the following steps: human cisplatin-resistant ovarian carcinoma SKOV3/DDP cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum (available from Gibco corporation, U.S.A.). The SKOV3/DDP cells in exponential growth phase were collected and PBS was resuspended to a suitable concentration (2X 107/ml) for subcutaneous tumor inoculation in nude mice. Female mice were inoculated with 100. Mu.l of cell suspension (containing 2X 106SKOV3/DDP cells) on the right armpit. When tumors grew to an average volume of about 50mm3, they were randomly grouped according to tumor size, and were dosed on the day of grouping, which was defined as day 0. Nude mice were dosed by oral gavage at a volume of 100 μl/nude mice. Tumor major diameter a and minor diameter b were measured every other day with vernier calipers. The subcutaneous SKOV3/DDP tumor volumes of the nude mice of each experimental group during the administration period are shown in FIG. 4.
TABLE 1 dosing regimen specifications
| Group of | Number of animals | Administration group | Dosage for administration | Administration mode | Period of administration |
| 1 | 6 | Vehicle control | - | Oral administration stomach lavage | Once dailyFor 18 consecutive days |
| 2 | 6 | CS-6(20mg/kg) | 20mg/kg | Oral administration stomach lavage | Once daily for 18 consecutive days |
The results of taking photographs of nude mice of each group of tumor growth in the human cisplatin-resistant ovarian cancer SKOV3/DDP cell subcutaneous transplantation tumor model 18 days after administration are shown in FIG. 4.
Experimental results: no nude mice die during the administration period and can tolerate the administration. On day 19 post-dosing, vehicle control tumor volumes 591.33 ±101.73mm3, end the trial, harvest and weigh the tumor. Tumor volume calculation formula: tumor volume (mm 3) =1/2× (a×b2) (where a represents the long diameter and b represents the short diameter). At the end of the trial, the mean tumor volume of the 20mg/kg treatment group of gamabufotalin was 267.46 ±137.33mm3, which was statistically significantly different (p=0.0033) compared to the control group (see fig. 4, 5).
Tumor samples were taken at the end of the experiment and tumor weights (g) were measured, with results consistent with tumor volume measurements. The tumors of each treatment group and control group are seen again in figure 6. Compared with the tumor weight of the solvent control (0.554+/-0.051 g), the tumor weight of 20mg/kg of the gamabufotalin after administration is 0.219+/-0.120 g, and the difference has obvious significance (P=0.0005). The result shows that the gamabufotalin has good in vivo anti-tumor activity in a platinum-resistant ovarian cancer transplantation tumor model.
Compared with the prior art, the invention has the following beneficial effects:
1. the examples of the present invention demonstrate the inhibition of proliferation of human platinum-resistant ovarian cancer cells by Xenopus for its CS-6.
2. The examples of the present invention demonstrate the therapeutic effect of gamabufotalin CS-6 on human platinum-resistant ovarian cancer animal models.
3. The embodiment of the invention can obviously reduce the volume and weight of human platinum drug-resistant ovarian cancer tumor after the administration of the gamabufotalin CS-6 (20 mg/kg-30 mg/kg), has obvious effect of inhibiting the platinum drug-resistant ovarian cancer tumor, can be applied to preparation of a platinum drug-resistant ovarian cancer treatment medicament, is applied to treatment of human platinum drug-resistant ovarian cancer, exploits a new application of gamabufotalin, and provides a choice for expanding a novel platinum drug-resistant ovarian cancer treatment medicament.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the invention.
Claims (6)
1. Application of gamabufotalin in preparing medicine for treating platinum-resistant ovarian cancer is provided.
2. Use of gamabufotalin according to claim 1 for the preparation of a medicament for the treatment of platinum resistant ovarian cancer, characterized in that: the structural formula of the gamabufotalin is shown as formula I:
3. use of gamabufotalin according to claim 1 for the preparation of a medicament for the treatment of platinum resistant ovarian cancer, characterized in that: can be administered alone or in combination with other therapies.
4. Use of gamabufotalin according to claim 3 for the preparation of a medicament for the treatment of platinum resistant ovarian cancer, characterized in that: the combined treatment comprises radiotherapy, chemotherapy and operation treatment.
5. Use of gamabufotalin according to claim 1 for the preparation of a medicament for the treatment of platinum resistant ovarian cancer, characterized in that: the gamabufotalin can be any pharmaceutically acceptable dosage form.
6. Use of gamabufotalin according to claim 1 for the preparation of a medicament for the treatment of platinum resistant ovarian cancer, characterized in that: the gamabufotalin may be in any pharmaceutically acceptable dosage.
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