Xiawa Mao1, Jiaquao Xiao1, Huifeng Wu1, Kefeng Ding2. 1. Urology Department, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province 310000, China. 2. Oncology Department, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province 310000, China.
Abstract
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 mean ± standard error from three independent experiments and analyzed by multiple t-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.
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 mean ± standard error from three independent experiments and analyzed by multiple t-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.
Authors: Maria Wartenberg; Edda Hoffmann; Heinrich Schwindt; Frank Grünheck; John Petros; J Rebecca S Arnold; Jürgen Hescheler; Heinrich Sauer Journal: FEBS Lett Date: 2005-08-15 Impact factor: 4.124
Authors: L Galluzzi; I Vitale; J M Abrams; E S Alnemri; E H Baehrecke; M V Blagosklonny; T M Dawson; V L Dawson; W S El-Deiry; S Fulda; E Gottlieb; D R Green; M O Hengartner; O Kepp; R A Knight; S Kumar; S A Lipton; X Lu; F Madeo; W Malorni; P Mehlen; G Nuñez; M E Peter; M Piacentini; D C Rubinsztein; Y Shi; H-U Simon; P Vandenabeele; E White; J Yuan; B Zhivotovsky; G Melino; G Kroemer Journal: Cell Death Differ Date: 2011-07-15 Impact factor: 15.828