https://scholars.lib.ntu.edu.tw/handle/123456789/585598
標題: | CDK7 inhibition by THZ1 suppresses cancer stemness in both chemonaïve and chemoresistant urothelial carcinoma via the hedgehog signaling pathway | 作者: | PO-MING CHOW Chang, Yu-Wei Kuo, Kuan-Lin WEI-CHOU LIN SHING-HWA LIU KUO-HOW HUANG |
關鍵字: | Apoptosis; Bladder cancer; Cancer stem cell; Cisplatin; Drug resistance | 公開日期: | 六月-2021 | 卷: | 507 | 來源出版物: | Cancer letters | 摘要: | Urothelial carcinoma (UC) is the most common type of bladder cancer, with a 5-year survival rate of only 4.6% in metastatic UC. Despite the advances related to immune-checkpoint inhibitor therapy, chemotherapy remains the standard of care for metastatic diseases, with a 50% response rate. The covalent cyclin-dependent kinase 7 (CDK7) inhibitor THZ1 interferes with transcription machinery and is reported to be effective in cancers without targetable mutations. Therefore, we investigated the therapeutic effect of THZ1 on UC and examined possible mechanisms underlying its effects in both chemonaïve and chemosensitive cancers. CDK7 expression is increased in bladder cancer tissues, especially in patients with chemoresistance. THZ1 induced apoptosis and decreased viability in RT4, BFTC905, HT1376, T24, and T24/R UC cell lines. RNA-sequencing, immunoblotting, and sphere-formation assays confirmed that THZ1 suppressed cancer stemness. In the mouse xenograft model, THZ1 suppressed both chemonaïve and chemoresistant tumors. These results indicate that CDK7 inhibition-related cancer stemness suppression is a potential therapeutic strategy for both chemonaïve and chemoresistant UC. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/585598 | ISSN: | 03043835 | DOI: | 10.1016/j.canlet.2021.03.012 | SDG/關鍵字: | cisplatin; cyclin dependent kinase 7; cyclin dependent kinase inhibitor; sonic hedgehog protein; thz 1; unclassified drug; antineoplastic agent; cisplatin; cyclin dependent kinase; cyclin-dependent kinase-activating kinase; phenylenediamine derivative; pr |
顯示於: | 醫學系 |
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