Autophagy inhibition enhances celecoxib-induced apoptosis in osteosarcoma

作者：Zhou, Pingting; Li, Yanyan; Li, Bo; Zhang, Meichao; Xu, Ci; Liu, Furao; Bian, Lei; Liu, Yuanhua; Yao, Yuan^*; Li, Dong^*

来源：Cell Cycle, 2018, 17(8): 997-1006.

DOI：10.1080/15384101.2018.1467677

• Celecoxib
• apoptosis
• autophagy
• osteosarcoma

Osteosarcoma (OS) is the most prevalent bone malignancy in childhood and adolescence, with highly aggressive and early systemic metastases. Here, we reported that celecoxib, a selective COX-2 inhibitor in the NSAID class, exhibits strong antitumor activity in dose dependent manner in two OS cell lines-143B and U2OS. We showed that celecoxib inhibits OS cell growth, causes G0/G1-phase arrest, modulates apoptosis and autophagy and reduces migration in OS cells. In addition, the results of fluorescent mitochondrial probe JC-1 test indicated that the mitochondrial pathway mediates celecoxib-induced apoptosis. Significantly, the autophagy inhibitor CQ combined with celecoxib causes greater cell proliferation inhibition and apoptosis. Pharmacologic inhibition of autophagy with another potent autophagy inhibitor SAR405 also enhances celecoxib-mediated suppression of cell viability. These results were confirmed with shRNAs targeting the autophagy-related gene Atg5. In OS tumor xenografts in vivo, celecoxib also presents antitumor activity. Taken together, our results shed light on the function and mechanism of antitumor action of celecoxib for treatment of OS patients.

• 出版日期2018
• 单位中国人民解放军第二军医大学; 南京医科大学; 上海交通大学; 江苏省肿瘤防治研究所; 天津市中医药研究院附属医院