down-regulation of glucose-regulated protein (grp) 78 potentiates cytotoxic effect of celecoxib in human urothelial carcinoma cells下调glucose-regulated蛋白(grp)78强化细胞毒性效应的塞来昔布在人类细胞移行细胞癌.pdfVIP

Down-Regulation of Glucose-Regulated Protein (GRP) 78 Potentiates Cytotoxic Effect of Celecoxib in Human Urothelial Carcinoma Cells 1,2 2 2 3 2 4 Kuo-How Huang *, Kuan-Lin Kuo , Shyh-Chyan Chen , Te-I Weng , Yuan-Ting Chuang , Yu-Chieh Tsai , Yeong-Shiau Pu2, Chih-Kang Chiang1,5, Shing-Hwa Liu1,2* 1 Graduate Institute of Toxicology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan, 2 Department of Urology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan, 3 Department of Forensic Medicine, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan, 4 Department of Oncology, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan, 5 Department of Integrated Diagnostics and Therapeutics, College of Medicine, National Taiwan University, and National Taiwan University Hospital, Taipei, Taiwan Abstract Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor that has been reported to elicit anti-proliferative response in various tumors. In this study, we aim to investigate the antitumor effect of celecoxib on urothelial carcinoma (UC) cells and the role endoplasmic reticulum (ER) stress plays in celecoxib-induced cytotoxicity. The cytotoxic effects were measured by MTT assay and flow cytometry. The cell cycle progression and ER stress-associated molecules were examined by Western blot and flow cytometry. Moreover, the cytotoxic effects of celecoxib combined with glucose-regulated protein (GRP) 78 knockdown (siRNA), (2)-epigallocatechin gallate (EGCG) or MG132 were assessed. We