Celecoxib-Induced Cytotoxic Effect Is Potentiated by Inhibition of Autophagy in Human Urothelial Carcinoma CellsReport as inadecuate




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Celecoxib, a cyclooxygenase-2 COX-2 inhibitor, can elicit anti-tumor effects in various malignancies. Here, we sought to clarify the role of autophagy in celecoxib-induced cytotoxicity in human urothelial carcinoma UC cells. The results shows celecoxib induced cellular stress response such as endoplasmic reticulum ER stress, phosopho-SAPK-JNK, and phosopho-c-Jun as well as autophagosome formation in UC cells. Inhibition of autophagy by 3-methyladenine 3-MA, bafilomycin A1 or ATG7 knockdown potentiated celecoxib-induced apoptosis. Up-regulation of autophagy by rapamycin or GFP-LC3B-transfection alleviated celecoxib-induced cytotoxicity in UC cells. Taken together, the inhibition of autophagy enhances therapeutic efficacy of celecoxib in UC cells, suggesting a novel therapeutic strategy against UC.



Author: Kuo-How Huang , Kuan-Lin Kuo , I-Lin Ho, Hong-Chiang Chang, Yuan-Ting Chuang, Wei-Chou Lin, Ping-Yi Lee, Shih-Chen Chang, Chih-Ka

Source: http://plos.srce.hr/



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