Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1α
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 bromi...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/8887437 |
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| _version_ | 1832560041255763968 |
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| author | Xiawa Mao Nanzhang Jiaquao Xiao Huifeng Wu Kefeng Ding |
| author_facet | Xiawa Mao Nanzhang Jiaquao Xiao Huifeng Wu Kefeng Ding |
| author_sort | Xiawa Mao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-73229dc74a9f44efadf8fa1a14d0ba53 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-73229dc74a9f44efadf8fa1a14d0ba532025-02-03T01:28:29ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/88874378887437Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1αXiawa Mao0Nanzhang1Jiaquao Xiao2Huifeng Wu3Kefeng Ding4Urology Department, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province 310000, ChinaUrology Department, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province 310000, ChinaUrology Department, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province 310000, ChinaUrology Department, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province 310000, ChinaOncology Department, The 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province 310000, ChinaPurpose. 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.http://dx.doi.org/10.1155/2021/8887437 |
| spellingShingle | Xiawa Mao Nanzhang Jiaquao Xiao Huifeng Wu Kefeng Ding Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1α Journal of Immunology Research |
| title | Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1α |
| title_full | Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1α |
| title_fullStr | Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1α |
| title_full_unstemmed | Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1α |
| title_short | Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1α |
| title_sort | hypoxia induced autophagy enhances cisplatin resistance in human bladder cancer cells by targeting hypoxia inducible factor 1α |
| url | http://dx.doi.org/10.1155/2021/8887437 |
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