Celecoxib-Induced Cytotoxic Effect Is Potentiated by Inhibition of Autophagy in Human Urothelial Carcinoma Cells

作者：Huang Kuo How^*; Kuo Kuan Lin; Ho I Lin; Chang Hong Chiang; Chuang Yuan Ting; Lin Wei Chou; Lee Ping Yi; Chang Shih Chen; Chiang Chih Kang; Pu Yeong Shiau; Chou Chien Tso; Hsu Chen Hsun; Liu Shing Hwa

来源：PLos One, 2013, 8(12): e82034.

DOI：10.1371/journal.pone.0082034

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.

• 出版日期2013-12-9