Purpose. To investigate the effect of hypoxia on chemoresistance and the underlying mechanism in bladder cancer cells. Methods. BIU-87 bladder cancer cell line was treated with cisplatin under hypoxic and normoxic conditions and tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blotting. All the data were expressed as from three independent experiments and analyzed by multiple -tests. Results. Apoptosis of bladder cancer cells caused by cisplatin was attenuated in hypoxic conditions. Hypoxia enhanced autophagy caused by cisplatin. The autophagy inhibitor and HIF-1α inhibitor can reverse the chemoresistance in hypoxic condition. Apoptosis and autophagy of bladder cancer cells were downregulated by HIF-1α inhibitor YC-1. Hypoxia-induced autophagy enhanced chemoresistance to cisplatin via the HIF-1 signaling pathway. Conclusion. Resistance to cisplatin in BIU-87 bladder cancer cells under hypoxic conditions can be explained by activation of autophagy, which is regulated by HIF-1α-associated signaling pathways. The hypoxia–autophagy pathway may be a target for improving the efficacy of cisplatin chemotherapy in bladder cancer.

中文翻译：

---

低氧诱导的自噬通过靶向低氧诱导因子 1α 增强人膀胱癌细胞的顺铂耐药性

目的。探讨缺氧对膀胱癌细胞化疗耐药的影响及其潜在机制。方法。BIU-87 膀胱癌细胞系在缺氧和常氧条件下用顺铂处理，并使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 测定法、流式细胞术和蛋白质印迹法进行测试. 所有数据均表示为来自三个独立的实验并通过多次测试进行分析。结果。由顺铂引起的膀胱癌细胞凋亡在缺氧条件下减弱。缺氧增强顺铂引起的自噬。自噬抑制剂和 HIF-1 α抑制剂可以逆转缺氧条件下的化学抗性。HIF- 1α抑制剂YC-1下调膀胱癌细胞的凋亡和自噬。缺氧诱导的自噬通过 HIF-1 信号通路增强对顺铂的化学抗性。结论。缺氧条件下 BIU-87 膀胱癌细胞对顺铂的耐药性可以通过自噬的激活来解释，自噬受 HIF-1 α调节相关的信号通路。缺氧-自噬途径可能是提高顺铂化疗治疗膀胱癌疗效的靶点。