دورية أكاديمية
Trifluoperazine, an Antipsychotic Drug, Effectively Reduces Drug Resistance in Cisplatin-Resistant Urothelial Carcinoma Cells via Suppressing Bcl-xL: An In Vitro and In Vivo Study
| العنوان: | Trifluoperazine, an Antipsychotic Drug, Effectively Reduces Drug Resistance in Cisplatin-Resistant Urothelial Carcinoma Cells via Suppressing Bcl-xL: An In Vitro and In Vivo Study |
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| المؤلفون: | Kuan-Lin Kuo, Shing-Hwa Liu, Wei-Chou Lin, Fu-Shun Hsu, Po-Ming Chow, Yu-Wei Chang, Shao-Ping Yang, Chung-Sheng Shi, Chen-Hsun Hsu, Shih-Ming Liao, Hong-Chiang Chang, Kuo-How Huang |
| المصدر: | International Journal of Molecular Sciences, Vol 20, Iss 13, p 3218 (2019) |
| بيانات النشر: | MDPI AG, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | urothelial carcinoma, trifluoperazine, chemotherapy resistance, Bcl-xL, apoptosis, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Cisplatin-based chemotherapy is the primary treatment for metastatic bladder urothelial carcinoma (UC). Most patients inevitably encounter drug resistance and resultant disease relapse. Reduced apoptosis plays a critical role in chemoresistance. Trifluoperazine (TFP), an antipsychotic agent, has demonstrated antitumor effects on various cancers. This study investigated the efficacy of TFP in inhibiting cisplatin-resistant bladder UC and explored the underlying mechanism. Our results revealed that cisplatin-resistant UC cells (T24/R) upregulated the antiapoptotic factor, B-cell lymphoma-extra large (Bcl-xL). Knockdown of Bcl-xL by siRNA resensitized cisplatin-resistant cells to the cisplatin cytotoxic effect. TFP (10−45 μM) alone elicited dose-dependent cytotoxicity, apoptosis, and G0/G1 arrest on T24/R cells. Co-treatment of TFP potentiated cisplatin-induced cytotoxicity in T24/R cells. The phenomenon that TFP alleviated cisplatin resistance to T24/R was accompanied with concurrent suppression of Bcl-xL. In vivo models confirmed that TFP alone effectively suppressed the T24/R xenograft in nude mice. TFP co-treatment enhanced the antitumor effect of cisplatin on the T24/R xenograft. Our results demonstrated that TFP effectively inhibited cisplatin-resistant UCs and circumvented cisplatin resistance with concurrent Bcl-xL downregulation. These findings provide a promising insight to develop a therapeutic strategy for chemoresistant UCs. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 |
| العلاقة: | https://www.mdpi.com/1422-0067/20/13/3218Test; https://doaj.org/toc/1422-0067Test |
| DOI: | 10.3390/ijms20133218 |
| الوصول الحر: | https://doaj.org/article/9b8d9677ddeb4c2ca8ed1f7c2cbe04d5Test |
| رقم الانضمام: | edsdoj.9b8d9677ddeb4c2ca8ed1f7c2cbe04d5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 |
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| DOI: | 10.3390/ijms20133218 |