CN113648308A - Application of oxfendazole as anti-ovarian cancer drug - Google Patents
Application of oxfendazole as anti-ovarian cancer drug Download PDFInfo
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- CN113648308A CN113648308A CN202111076316.5A CN202111076316A CN113648308A CN 113648308 A CN113648308 A CN 113648308A CN 202111076316 A CN202111076316 A CN 202111076316A CN 113648308 A CN113648308 A CN 113648308A
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- 206010033128 Ovarian cancer Diseases 0.000 title claims abstract description 63
- 206010061535 Ovarian neoplasm Diseases 0.000 title claims abstract description 63
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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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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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- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of medicines, and particularly relates to application of oxfendazole as an anti-ovarian cancer medicine, wherein for researching and developing a new anti-ovarian cancer medicine, research shows that the oxfendazole can obviously inhibit the activity of ovarian cancer cells from different sources; and can inhibit the proliferation of ovarian cancer cells and induce the apoptosis of ovarian cancer cells; the oxfendazole is proved to have good ovarian cancer resistance effect, and is expected to be developed into a novel medicament for efficiently treating ovarian cancer, so that the novel application of the oxfendazole is explored, and a novel medicament and a novel approach are provided for treating the ovarian cancer.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of oxfendazole as an anti-ovarian cancer medicine.
Background
Ovarian cancer is a common malignancy of the female reproductive system, and in recent years, the incidence and mortality of ovarian cancer have been on the rise. Worldwide, ovarian cancer has its prevalence at position 3 among female reproductive malignancies and a high mortality rate at position 2. At present, ovarian cancer is mainly treated by adopting a comprehensive treatment method of surgery and chemotherapy. As for chemotherapy, with the continuous development of modern medical research, chemotherapy drugs for treating ovarian cancer are continuously developed, and the chemotherapy drugs for clinically treating ovarian cancer mainly comprise paclitaxel, carboplatin, doxorubicin and the like. The application of the chemotherapy drug can obviously improve the survival rate of ovarian cancer patients. However, the treatment effect of the chemotherapeutic drugs is still unsatisfactory due to the limitations of problems such as non-response to chemotherapy, tolerance to chemotherapy, toxic and side effects and the like, and the 5-year survival rate of patients with advanced ovarian cancer is only 20% -30%. Therefore, the search for new drugs for treating ovarian cancer is very slow.
Oxfendazole (Oxfendazole) with the chemical name of 5-phenylsulfonyl-benzimidazole-2-methyl carbamate and the molecular formula of C15H13N3O3S, molecular weight is 315.35, and is a novel high-efficiency, broad-spectrum and low-toxicity benzimidazole carbamate anthelmintic. The oxfendazole can inhibit an electron transfer system of a worm mitochondrion and a phosphorylation reaction coupled with the electron transfer system, inhibit ATP synthesis, and block a glucose transport system, so that the function of a microtubule depending on the glucose transport system is inhibited, and finally, a killing effect is generated on worms. At present, no report on the ovarian cancer resistance of oxfendazole exists.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides the application of oxfendazole as an anti-ovarian cancer medicament, not only explores the new application of oxfendazole, but also provides a new medicament and a new way for treating ovarian cancer.
In order to achieve the purpose, the invention adopts the technical scheme that:
the invention provides application of oxfendazole in preparation of an anti-ovarian cancer drug.
The invention also provides application of oxfendazole in preparation of a medicine for inhibiting ovarian cancer cell viability.
Preferably, the ovarian cancer cells comprise a2780 cells, OVCAR3 cells, SKOV3 cells, and KGN cells.
According to research, the oxfendazole can obviously inhibit the activity of ovarian cancer cells from different sources; and can inhibit the proliferation of ovarian cancer cells and induce the apoptosis of ovarian cancer cells; proves that the oxfendazole has good ovarian cancer resistance effect and is expected to be developed into a novel medicament for efficiently treating ovarian cancer.
The invention also provides an anti-ovarian cancer medicament which takes the oxfendazole as a main active ingredient.
The invention also provides a medicine for inhibiting the activity of ovarian cancer cells, which takes the oxfendazole as a main active ingredient.
Preferably, the two medicaments also comprise other effective components which are compatible with the oxfendazole to play a synergistic effect.
Preferably, the two medicaments according to the above further comprise a pharmaceutically acceptable carrier and/or excipient. The two medicines can be mixed with pharmaceutically acceptable carriers or excipients to prepare the composition.
Further, the excipient refers to diluents, binders, lubricants, disintegrants, solubilizing agents, stabilizers and the like which can be used in the pharmaceutical field, and some pharmaceutical bases. The carrier is a functional pharmaceutical adjuvant which can be obtained in the field of medicines, and comprises a surfactant, a suspending agent, an emulsifier and some novel pharmaceutical high polymer materials, such as cyclodextrin, chitosan, polylactic acid (PLA), polyglycolic acid polylactic acid copolymer (PLGA), hyaluronic acid and the like.
Preferably, according to the two medicaments, the dosage forms of the medicaments comprise tablets, capsules, granules, dropping pills, infusion solutions and injections.
Further, the above dosage forms refer to clinically usual dosage forms. Pharmaceutical formulations may be administered orally or parenterally (e.g., intravenously, subcutaneously, intraperitoneally, or topically) and, if certain drugs are unstable under gastric conditions, may be formulated as enteric coated tablets.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a new application of oxfendazole in resisting ovarian cancer. According to research, the oxfendazole can obviously inhibit the activity of ovarian cancer cells from different sources; and can inhibit the proliferation of ovarian cancer cells and induce the apoptosis of ovarian cancer cells; the oxfendazole is proved to have good ovarian cancer resistance effect, and is expected to be developed into a novel medicament for efficiently treating ovarian cancer, so that the novel application of the oxfendazole is explored, and a novel medicament and a novel approach are provided for treating the ovarian cancer.
Drawings
FIG. 1 shows the inhibitory effect of oxfendazole at different concentrations on the viability of ovarian cancer cells;
FIG. 2 shows the inhibitory effect of oxfendazole on the proliferative capacity of ovarian cancer cells at various concentrations;
figure 3 is a graph of the effect of oxfendazole in inducing apoptosis in ovarian cancer cells.
Detailed Description
The following further describes the embodiments of the present invention. It should be noted that the description of the embodiments is provided to help understanding of the present invention, but the present invention is not limited thereto. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The experimental procedures in the following examples were carried out by conventional methods unless otherwise specified, and the test materials used in the following examples were commercially available by conventional methods unless otherwise specified.
Experimental example 1 inhibitory Effect of Oxfendazole on ovarian cancer cell viability
Ovarian cancer cells (a2780, OVCAR3, SKOV3, and KGN) in logarithmic growth phase purchased from beina bio were seeded in 96-well plates at 5000 cells per well in 200 μ L RPMI-1640 medium. Drug treatment group, control group and blank group were set separately. Wherein, the drug treatment group is a group (10 μ M, 25 μ M, 50 μ M, 100 μ M) containing oxfendazole with different concentrations, the control group only contains cells without drugs, and the blank group does not contain cells but only contains culture medium. Drug-treated group cells were treated with drug for 48h, 4h before the end of treatment, 20 μ L of CCK8 solution was added to each well and incubation was continued for 4 h. Then, reading an absorbance value at the wavelength of 450nm by using a full-wavelength multifunctional microplate reader, and calculating the cell activity according to the following formula by using the absorbance value:
cell viability ═ 100% (drug treatment OD-blank OD)/(control OD-blank OD). Wherein the cell viability is half inhibitory solubility (IC)50) Calculated using Graphpad software.
As shown in the results of fig. 1, oxfendazole inhibited ovarian cancer cell viability.
Experimental example 2 inhibitory Effect of Oxfendazole on proliferation potency of ovarian cancer cells
Ovarian cancer cells (a2780) in log phase were seeded in six-well plates at 500 cells per well in 200 μ L of medium. Cells were treated with different concentrations of oxfendazole (7.5 μ M and 10 μ M) for 7 days after the cells were fully adherent. The culture medium was changed every 3 days during the process. After treatment the cells were discarded from the medium, washed 2 times with PBS, fixed with ice bath methanol for 5min and stained with crystal violet.
As shown in the results of fig. 2, oxfendazole inhibited the proliferative capacity of ovarian cancer cells.
Experimental example 3 Induction of apoptosis in ovarian cancer cells by Oxfendazole
Ovarian cancer cells (A2780) in the logarithmic growth phase were treated with oxfendazole (5. mu.M and 10. mu.M) at different concentrations for 48h, then digested with EDTA-free trypsin for 2min to single cells, centrifuged at 2000rpm for 5min after digestion, and washed 2 times with PBS. Then, the apoptosis detection kit working solution (500. mu.L of apoptosis buffer, 5. mu.L of Annexin V-FITC dye and 5. mu.L of PI dye) purchased from Kyowa Kai Biotechnology Co., Ltd is added to the cells, and the cells are scattered, mixed uniformly and placed in the dark for reaction for 15 min. The apoptosis rate was measured using a BD FACSCAnto II flow cytometer. Wherein, cells which are Annexin V-FITC single positive and Annexin V-FITC/PI double positive are apoptosis cells.
As shown in the results of fig. 3, oxfendazole induced apoptosis in ovarian cancer cells.
The embodiments of the present invention have been described in detail, but the present invention is not limited to the described embodiments. It will be apparent to those skilled in the art that various changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, and the scope of protection is still within the scope of the invention.
Claims (8)
1. Application of oxfendazole in preparation of anti-ovarian cancer drugs.
2. Application of oxfendazole in preparation of medicines for inhibiting ovarian cancer cell viability.
3. The use of claim 2, wherein the ovarian cancer cells comprise A2780 cells, OVCAR3 cells, SKOV3 cells, and KGN cells.
4. An anti-ovarian cancer drug, which is characterized by taking oxfendazole as a main active ingredient.
5. A drug for inhibiting the activity of ovarian cancer cells, which is characterized by comprising oxfendazole as a main active ingredient.
6. The anti-ovarian cancer drug of claim 4 or the ovarian cancer cell viability-inhibiting drug of claim 5, further comprising other active ingredients that are synergistic with oxfendazole.
7. An anti-ovarian cancer drug according to claim 4 or an ovarian cancer cell viability-inhibiting drug according to claim 5, further comprising a pharmaceutically acceptable carrier and/or excipient.
8. The anti-ovarian cancer drug of claim 4 or the drug for inhibiting ovarian cancer cell viability of claim 5, wherein the dosage form of the drug comprises tablet, capsule, granule, drop pill, infusion solution and injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111076316.5A CN113648308A (en) | 2021-09-14 | 2021-09-14 | Application of oxfendazole as anti-ovarian cancer drug |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111076316.5A CN113648308A (en) | 2021-09-14 | 2021-09-14 | Application of oxfendazole as anti-ovarian cancer drug |
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2342470A1 (en) * | 2001-03-30 | 2002-09-30 | David Lawson Morris | Method for treatment of cancer and benzimidazole compositions for use therein |
| CA2441768A1 (en) * | 2001-03-26 | 2002-10-03 | Unisearch Limited | Method for treatment of cancer and compositions for use therein |
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| WO2004006849A2 (en) * | 2002-07-15 | 2004-01-22 | Combinatorx, Incorporated | Combinations of drugs for the treatment of neoplasms |
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-
2021
- 2021-09-14 CN CN202111076316.5A patent/CN113648308A/en active Pending
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| WO2004006849A2 (en) * | 2002-07-15 | 2004-01-22 | Combinatorx, Incorporated | Combinations of drugs for the treatment of neoplasms |
| CN101035530A (en) * | 2004-08-31 | 2007-09-12 | 新南部创新有限公司 | VEGF inhibition |
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| Title |
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