Tripterygium glycosides reverse chemotherapy resistance in ovarian cancer by targeting the NRF2/GPX4 signal axis to induce ferroptosis of drug-resistant human epithelial ovarian cancer cells

雷公藤多苷通过靶向 NRF2/GPX4 信号轴诱导耐药人上皮性卵巢癌细胞铁死亡逆转卵巢癌化疗耐药性

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作者:Bo Ma, Yanying Zhong, Runqiu Chen, Xinlu Zhan, Genhua Huang, Yifei Xiong, Buzhen Tan

Abstract

Cisplatin resistance is the main cause of postoperative recurrence and difficulty in the treatment of ovarian cancer. It is urgently needed to identify therapeutic drugs with unique functions to overcome the current challenges in the treatment of ovarian cancer. In this study, we found that TG promoted the accumulation of ROS and MDA in A2780/DDP cells and downregulated the expression of key antioxidant molecules. In vivo, the survival rate of tumor-bearing nude mice was prolonged by TG without significant hepatotoxic reaction. The expression of key antioxidant molecules in tumor tissues was consistent with that in vitro. These findings revealed that TG disrupted homeostasis of redox reactions and induced ferroptosis in A2780/DDP cells, thereby enhancing cisplatin chemosensitivity of ovarian cancer. Overall, TG may be a novel potential therapeutic option for reversing resistance to cisplatin chemotherapy.

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