https://scholars.lib.ntu.edu.tw/handle/123456789/625392
標題: | Cigarette Smoke Containing Acrolein Contributes to Cisplatin Resistance in Human Bladder Cancers through the Regulation of HER2 Pathway or FGFR3 Pathway | 作者: | JIAN-HUA HONG Tong Z.-J Wei T.-E YU-CHUAN LU Huang C.-Y CHAO-YUAN HUANG Chiang C.-H FU-SHAN JAW Cheng H.-W Wang H.-T. |
公開日期: | 2022 | 卷: | 21 | 期: | 6 | 起(迄)頁: | 1010-1019 | 來源出版物: | Molecular Cancer Therapeutics | 摘要: | Cisplatin-based chemotherapy is the first-line therapy for bladder cancer. However, cisplatin resistance has been associated with the recurrence of bladder cancer. Previous studies have shown that activation of FGFR and HER2 signaling are involved in bladder cancer cell proliferation and drug resistance. Smoking is the most common etiologic risk factor for bladder cancer, and there is emerging evidence that smoking is associated with cisplatin resistance. However, the underlying mechanism remains elusive. Acrolein, a highly reactive aldehyde, is abundant in tobacco smoke, cooking fumes, and automobile exhaust fumes. Our previous studies have shown that acrolein contributes to bladder carcinogenesis through the induction of DNA damage and inhibition of DNA repair. In this study, we found that acrolein induced cisplatin resistance and tumor progression in both non–muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) cell lines RT4 and T24, respectively. Activation of HER2 and FGFR3 signaling contributes to acrolein-induced cisplatin resistance in RT4 and T24 cells, respectively. Furthermore, trastuzumab, an anti-HER2 antibody, and PD173074, an FGFR inhibitor, reversed cisplatin resistance in RT4 and T24 cells, respectively. Using a xenograft mouse model with acrolein-induced cisplatin-resistant T24 clones, we found that cisplatin combined with PD173074 significantly reduced tumor size compared with cisplatin alone. These results indicate that differential molecular alterations behind cisplatin resistance in NMIBC and MIBC significantly alter the effectiveness of targeted therapy combined with chemotherapy. This study provides valuable insights into therapeutic strategies for cisplatin-resistant bladder cancer. © 2022 American Association for Cancer Research |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85131218899&doi=10.1158%2f1535-7163.MCT-21-0725&partnerID=40&md5=85f0343b39cd9835f0b2a0b1c3a1ecbd https://scholars.lib.ntu.edu.tw/handle/123456789/625392 |
ISSN: | 15357163 | DOI: | 10.1158/1535-7163.MCT-21-0725 | SDG/關鍵字: | acrolein; antineoplastic agent; cisplatin; FGFR3 protein, human; fibroblast growth factor receptor 3; animal; bladder tumor; cigarette smoking; drug resistance; genetics; human; mouse; pathology; tumor cell line; Acrolein; Animals; Antineoplastic Agents; Cell Line, Tumor; Cigarette Smoking; Cisplatin; Drug Resistance, Neoplasm; Humans; Mice; Receptor, Fibroblast Growth Factor, Type 3; Urinary Bladder Neoplasms |
顯示於: | 醫學工程學研究所 |
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