https://scholars.lib.ntu.edu.tw/handle/123456789/620622
標題: | The UCHL5 inhibitor b-AP15 overcomes cisplatin resistance via suppression of cancer stemness in urothelial carcinoma | 作者: | PO-MING CHOW Dong, Jun-Ren Chang, Yu-Wei Kuo, Kuan-Lin WEI-CHOU LIN SHING-HWA LIU KUO-HOW HUANG |
關鍵字: | ER stress; bladder cancer; cancer stem cell; chemoresistance; deubiquitination | 公開日期: | 15-九月-2022 | 出版社: | Cell Press | 卷: | 26 | 起(迄)頁: | 387-398 | 來源出版物: | Molecular Therapy Oncolytics | 摘要: | Urothelial carcinoma (UC) comprises the majority of bladder cancers. Standard platinum-based chemotherapy has a response rate of approximately 50%, but drug resistance develops after short-term treatment. Deubiquitinating (DUB) enzyme inhibitors increase protein polyubiquitination and endoplasmic reticulum (ER) stress, which might further suppress cancer stemness and overcome cisplatin resistance. Therefore, we investigated the cytotoxic effect and potential mechanisms of b-AP15 on urothelial carcinoma. Our results revealed that b-AP15 induced ER stress and apoptosis in BFTC905, T24, T24/R (cisplatin-resistant), and RT4 urothelial carcinoma cell lines. Inhibition of the MYC signaling pathway and cancer stemness by b-AP15 was confirmed by RNA sequencing, RT-PCR, immunoblotting, and sphere-forming assays. In the mouse xenograft model, the combination of b-AP15 and cisplatin showed superior therapeutic effects compared with either monotherapy. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/620622 | ISSN: | 2372-7705 | DOI: | 10.1016/j.omto.2022.08.004 |
顯示於: | 醫學系 |
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