CN-121971433-A - Application of 2-phenyl oxindole in preparation of drugs for reversing cisplatin resistance or treating tumors

Abstract

The invention belongs to the technical field of tumor drug research, and in particular relates to an application of 2-phenyl oxindole in preparation of drugs for reversing cisplatin resistance or treating tumors. The in vitro experiment and the in vivo experiment prove that the 2-phenyl oxindole can effectively inhibit proliferation of triple negative breast cancer cells, can obviously improve sensitivity of the cells to a series of cisplatin concentrations, and the organ histopathological staining result of mice shows that the 2-phenyl oxindole does not cause obvious main organ injuries such as liver, kidney and the like.

Inventors

• LIU PEIJUN
• LIU JIE
• ZHANG JINGYUE
• ZHANG HUIWEN
• LIU NANXIN

Assignees

• 西安交通大学医学院第一附属医院

Dates

Publication Date

20260505

Application Date

20260316

Claims (9)

1. 1. Use of 2-phenyloxindole in the manufacture of a medicament for reversing cisplatin resistance or treating a tumor.
2. 2. The use according to claim 1, wherein the 2-phenyloxindole is used in combination with cisplatin for the treatment of tumors.
3. 3. The use according to any one of claims 1-2, wherein the tumor is breast cancer.
4. 4. The use of claim 3, wherein the breast cancer comprises triple negative breast cancer.
5. 5. The use according to claim 4, wherein the breast cancer cell line is MDA-MB-231 cells or SUM159 cells or 4T1 cells.
6. 6. A pharmaceutical composition comprising a therapeutically effective amount of 2-phenyloxindole and cisplatin of claim 1, and a pharmaceutically acceptable adjuvant.
7. 7. The pharmaceutical composition according to claim 6, wherein the mass ratio of the 2-phenyloxindole to the cisplatin is 1:0.4-25.6.
8. 8. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition is used for reversing the resistance of tumor cells to cisplatin or for treating tumors.
9. 9. The pharmaceutical composition of claim 8, wherein the tumor is breast cancer.

Description

Application of 2-phenyl oxindole in preparation of drugs for reversing cisplatin resistance or treating tumors Technical Field The invention belongs to the technical field of tumor drug research, and in particular relates to an application of 2-phenyl oxindole in preparation of drugs for reversing cisplatin resistance or treating tumors. Background Cisplatin (CISPLATIN) is one of the most widely used platinum chemotherapeutics in clinic, and has remarkable curative effects on various solid tumors such as ovarian cancer, testicular cancer, head and neck cancer, lung cancer, breast cancer and the like. However, its clinical application is limited by two major factors, namely, its inherent serious side effects such as nephrotoxicity, neurotoxicity and ototoxicity, and its susceptibility to acquired drug resistance by tumor cells. Resistance of tumor cells to cisplatin is a key cause of chemotherapy failure and recurrent tumor metastasis. The mechanism is extremely complex, and relates to a plurality of aspects such as reduction of intracellular medicine intake, increase of efflux, enhancement of DNA damage repair capability, apoptosis escape, change of tumor microenvironment and the like. At present, strategies for overcoming cisplatin resistance mainly comprise development of novel platinum drugs, combined use of other chemotherapeutics or targeting drugs, and application of chemical sensitizers capable of reversing a drug resistance mechanism. However, most of the existing drug resistance reversing strategies or effects are limited, or have superimposed toxic and side effects, or face new drug resistance problems. Therefore, development of a cisplatin drug resistance reversal agent with high efficiency and low toxicity, in particular to a compound which can interfere with a drug resistance mechanism from multiple ways and has direct anti-tumor activity, is a great subject to be solved urgently in the field of tumor treatment at present. 2-Phenyloxindole (2-Phenylisatogen, 2-PIO) is a known intermediate in organic synthesis, and has relatively limited research on biological activity. In the prior published literature, no report on clear and remarkable efficacy of 2-phenyl oxindole in resisting tumors, particularly in reversing the drug resistance of tumor cells to cisplatin is yet seen. Disclosure of Invention Based on the technical problems, the invention provides an application of 2-phenyl oxindole in preparing a medicament for reversing cisplatin resistance or treating tumors. In vitro experiments and in vivo experiments prove that the 2-phenyl oxindole can effectively inhibit proliferation of triple negative breast cancer cells and can remarkably improve sensitivity of the cells to cisplatin. The invention provides an application of 2-phenyl oxindole in preparing a medicine for reversing drug resistance of tumor cells to cisplatin. The invention provides an application of 2-phenyl oxindole in preparing a medicine for treating tumor. As a preferred embodiment of the present invention, the 2-phenyloxindole is used in combination with cisplatin. As a preferred embodiment of the present invention, the tumor is breast cancer. As a preferred embodiment of the present invention, the breast cancer includes triple negative breast cancer. As a preferred embodiment of the invention, the breast cancer cell line is MDA-MB-231 cells or SUM159 cells or 4T1 cells. The invention provides a pharmaceutical composition, which comprises 2-phenyl oxindole and cisplatin with effective treatment dose and pharmaceutically acceptable auxiliary materials. As a preferred embodiment of the invention, the mass ratio of the 2-phenyl oxindole to the cisplatin is 1:0.4-25.6. As a preferred embodiment of the invention, the pharmaceutical composition is used for reversing the resistance of tumor cells to cisplatin or for treating tumors. As a preferred embodiment of the present invention, the tumor is breast cancer. Further preferably, the breast cancer comprises triple negative breast cancer. Compared with the prior art, the technical scheme provided by the invention has the following remarkable advantages and beneficial effects: The invention discloses and proves that the compound 2-phenyl oxindole has the novel application of reversing the drug resistance of tumor cells (especially breast cancer cells) to cisplatin for the first time. Meanwhile, the anti-tumor activity of the single-use drug is also clarified, and a candidate drug molecule is provided for tumor treatment, especially overcoming the clinical problem of cisplatin resistance. The invention discovers that when the 2-phenyl oxindole is used in combination with cisplatin, the killing effect of cisplatin on drug-resistant tumor cells can be obviously enhanced. In vitro experiment results show that in the presence of 2-phenyl oxindole, half inhibition concentration of cisplatin to MDA-MB-231 and SUM159 cells is obviously reduced, and cell viability curve is obviously shifted to