Cinobufagin regulates the microRNA-149-3p/AFF4 axis to affect the proliferation and apoptosis of cisplatin-resistant ovarian cancer cells.

IF 1.9 4区医学 Q3 INFECTIOUS DISEASES

Journal of Chemotherapy Pub Date : 2025-05-27 DOI:10.1080/1120009X.2025.2508614

Yunfei Liu, Taoli Chen, Yanpeng Wang, Yuanyuan Gao, Ning Xie, Wanping Xia, Qichuan Wang

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引用次数: 0

Abstract

Although cinobufagin has been demonstrated to inhibit the growth of various malignant tumors, its functional role in ovarian cancer remains unclear. In light of this, the present study aims to thoroughly investigate the effects of cinobufagin on ovarian cancer progression and elucidate its underlying molecular mechanisms, thereby providing novel insights into future therapeutic strategies. A2780/DDP, a cisplatin-resistant cell line for ovarian cancer, was treated with gradient doses of cinobufagin. The microRNA-149-3p and AFF4 binding sites were predicted by bioinformatics. In cisplatin-resistant ovarian cancer cells, microRNA-149-3p and AFF4 expression were detected using qRT-PCR, and the binding association between microRNA-149-3p and AFF4 was confirmed by dual-luciferase and RIP assays. Cell viability was assessed using the CCK-8 test, cell proliferation was identified using the EdU assay and colony formation, and cell apoptosis was identified using flow cytometry. The results showed that cinobufagin inhibited the proliferation and promoted apoptosis of cisplatin-resistant ovarian cancer cells. microRNA-149-3p was highly expressed in cisplatin-resistant ovarian cancer cells, while AFF4 was lowly expressed in these cells. Overexpression of microRNA-149-3p promoted the proliferation and inhibited the apoptosis of cisplatin-resistant ovarian cancer cells, which was reversed by the addition of cinobufagin. Overexpression of AFF4 suppressed proliferation and promoted apoptosis of cisplatin-resistant ovarian cancer cells. MicroRNA-149-3p repressed AFF4 expression, and partial attenuation of the effects of AFF4 overexpression on cell phenotype was observed when microRNA-149-3p was overexpressed. In conclusion,cinobufagin regulated microRNA-149-3p/AFF4 axis to inhibit proliferation of ovarian cancer cells and promote cell apoptosis. Targeting the microRNA-149-3p/AFF4 axis with cinobufagin could represent a novel therapeutic strategy for ovarian cancer.

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Cinobufagin调节microRNA-149-3p/AFF4轴影响顺铂耐药卵巢癌细胞的增殖和凋亡。

尽管蟾毒蛋白已被证明能抑制多种恶性肿瘤的生长，但其在卵巢癌中的功能作用尚不清楚。鉴于此，本研究旨在深入研究蟾毒球蛋白对卵巢癌进展的影响，并阐明其潜在的分子机制，从而为未来的治疗策略提供新的见解。A2780/DDP是一种卵巢癌顺铂耐药细胞系，用梯度剂量的cinobufagin治疗。利用生物信息学方法预测了microRNA-149-3p和AFF4的结合位点。在顺铂耐药卵巢癌细胞中，采用qRT-PCR检测microRNA-149-3p和AFF4的表达，并通过双荧光素酶和RIP检测证实microRNA-149-3p与AFF4的结合关系。CCK-8检测细胞活力，EdU检测细胞增殖和集落形成，流式细胞术检测细胞凋亡。结果表明，蟾毒球蛋白抑制顺铂耐药卵巢癌细胞增殖，促进细胞凋亡。microRNA-149-3p在顺铂耐药卵巢癌细胞中高表达，而AFF4在顺铂耐药卵巢癌细胞中低表达。过表达microRNA-149-3p可促进顺铂耐药卵巢癌细胞增殖，抑制细胞凋亡，而加入蟾毒球蛋白可逆转这一作用。AFF4过表达抑制顺铂耐药卵巢癌细胞增殖，促进细胞凋亡。MicroRNA-149-3p可抑制AFF4的表达，而当MicroRNA-149-3p过表达时，AFF4过表达对细胞表型的影响部分减弱。综上所述，cinobufagin通过调控microRNA-149-3p/AFF4轴抑制卵巢癌细胞增殖，促进细胞凋亡。用cinobufagin靶向microRNA-149-3p/AFF4轴可能是一种新的卵巢癌治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Chemotherapy 医学-药学

CiteScore

3.70

自引率

0.00%

发文量

144

审稿时长

6-12 weeks

期刊介绍： The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy. The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs. Specific areas of focus include, but are not limited to: · Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents; · Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy; · Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents; · The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs; · Drug interactions in single or combined applications; · Drug resistance to antimicrobial and anticancer drugs; · Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research; · Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs; · Pharmacogenetics and pharmacogenomics; · Precision medicine in infectious disease therapy and in cancer therapy; · Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.