Application of cucurbitacine B and derivatives thereof in preparation of anti-tumor drug-resistant drugs

Abstract

The invention discloses application of cucurbitacin B and a derivative thereof in preparation of an anti-tumor drug-resistant drug. It is found that the cucurbitacin B inhibits proliferation of an ovarian cancer cis-platinum drug-resistant cell strain, and the IC50 values of the cucurbitacin B to C13 * and A2780DDP cells are 64.28 + / -14.54 nM and 29.20 + / -2.26 nM respectively; the apoptosis of C13 * cells is promoted, and invasion and migration of the C13 * cells are inhibited; and PI3K / Akt signal channels in C13 * and A2780DDP cells are inhibited. Therefore, the cucurbitacine B is applied to preparation of anti-tumor drug-resistant drugs. The cucurbitacine B has a good development prospect.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular to the application of cucurbitacin B and its derivatives in the preparation of anti-tumor drug resistance. Background technique [0002] The biological learning of ovarian cancer is different from other gynecological malignancies. The early clinical symptoms are not obvious. Most patients have a large amount of ascites and pelvic tumors when they go to the doctor. Because ovarian cancer is insidious and often confined to the abdominal cavity, more than two-thirds of patients are diagnosed at an advanced stage. Surgery combined with chemotherapy improves the short-term efficacy of advanced ovarian cancer patients, but there is still a 70%-80% recurrence rate. According to the 2021 NCCN Clinical Practice Guidelines for Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer (1st Edition), for patients with stage II-IV ovarian cancer, chemotherapy with combination of ca...

AI Technical Summary

Problems solved by technology

Cisplatin, as the first-generation platinum-based antitumor drug, lacks selectivity for tumor tissue and has serious side effects

Although carboplatin in the second-generation platinum drug has good chemical stability and is 17 times more water-soluble than cisplatin, it has the same carrier group as cisplatin. For patients who develop resistance to cisplatin, use carboplatin Doesn't work as well with platinum

Oxaliplatin, one of the third-generation platinum drugs, has avoided some of the resistance mechanisms of cisplatin (such as mismatch repair defects and bypass replication mechanisms), but it has not completely solved the problem of platinum resistance

Lobaplatin, one of the third-generation platinum drugs, not only affects the synthesis and replication of DNA, but also affects the expression of the original tumor gene c-myc, and has not improved the problem of platinum drug resistance.

Even in tumors highly relevant for proliferation and survival of this signaling cascade, inhibitor toxicity at certain doses results in short-lived and incomplete target engagement

Third, inhibitors of this pathway often lead to rapid and tissue-dependent activation of molecular feedback loops, limiting the long-term effectiveness of these drugs

Why are most PI3K targeting inhibitors unable to enter the clinic? At present, it is generally believed that PI3K / AKT / mTOR signaling is widely expressed in the body, resulting in narrow therapeutic windows and high cytotoxicity of most compounds, hindering their clinical application

At the same time, the tumor itself can reactivate drug targets or mutate drug targets, induce cross-signaling pathways, and lead to drug resistance

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