Yunfei Liu, Taoli Chen, Yanpeng Wang, Yuanyuan Gao, Ning Xie, Wanping Xia, Qichuan Wang
{"title":"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。","authors":"Yunfei Liu, Taoli Chen, Yanpeng Wang, Yuanyuan Gao, Ning Xie, Wanping Xia, Qichuan Wang","doi":"10.1080/1120009X.2025.2508614","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"1-10"},"PeriodicalIF":1.9000,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cinobufagin regulates the microRNA-149-3p/AFF4 axis to affect the proliferation and apoptosis of cisplatin-resistant ovarian cancer cells.\",\"authors\":\"Yunfei Liu, Taoli Chen, Yanpeng Wang, Yuanyuan Gao, Ning Xie, Wanping Xia, Qichuan Wang\",\"doi\":\"10.1080/1120009X.2025.2508614\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":15338,\"journal\":{\"name\":\"Journal of Chemotherapy\",\"volume\":\" \",\"pages\":\"1-10\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Chemotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/1120009X.2025.2508614\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/1120009X.2025.2508614","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Cinobufagin regulates the microRNA-149-3p/AFF4 axis to affect the proliferation and apoptosis of cisplatin-resistant ovarian cancer cells.
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.
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.
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