KUO-HOW HUANGKuo K.-L.Ho I.-L.HONG-CHIANG CHANGChuang Y.-T.WEI-CHOU LINLee P.-Y.Chang S.-C.CHIH-KANG CHIANGYEONG-SHIAU PUChou C.-T.Hsu C.-H.Liu S.-H.2021-01-262021-01-2620131932-6203https://www.scopus.com/inward/record.uri?eid=2-s2.0-84891934329&doi=10.1371%2fjournal.pone.0082034&partnerID=40&md5=e1cd01a523db39d9241f4a3805b67ef1https://scholars.lib.ntu.edu.tw/handle/123456789/541961Celecoxib, 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-LC3Btransfection 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. Copyright: ? 2013 Huang et al.[SDGs]SDG33 methyladenine; autophagy protein 5; bafilomycin A1; celecoxib; cyclooxygenase 2; green fluorescent protein; Janus kinase; mammalian target of rapamycin inhibitor; mitogen activated protein kinase; phosphatidylinositol 3 kinase; rapamycin; small interfering RNA; stress activated protein kinase; antineoplastic activity; apoptosis; article; autophagosome; autophagy; cancer cell culture; cell culture; cell viability; controlled study; drug cytotoxicity; endoplasmic reticulum stress; enzyme inhibition; flow cytometry; human; human cell; transitional cell carcinoma; upregulation; Adenine; Antineoplastic Agents; Autophagy; Carcinoma, Transitional Cell; Cell Line, Tumor; Cyclooxygenase 2 Inhibitors; Endoplasmic Reticulum Stress; Gene Expression Regulation, Neoplastic; Humans; JNK Mitogen-Activated Protein Kinases; Macrolides; MAP Kinase Kinase 4; Phosphoproteins; Pyrazoles; RNA, Small Interfering; Signal Transduction; Sirolimus; Sulfonamides; Ubiquitin-Activating Enzymes; Urinary Bladder Neoplasmsjournal article10.1371/journal.pone.0082034243491762-s2.0-84891934329