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Potent cell growth inhibitory effects in hepatitis B virus X protein positive hepatocellular carcinoma cells by the selective cyclooxygenase‐2 inhibitor celecoxib
Author(s) -
Xie Huahong,
Gao Liucun,
Chai Na,
Song Jiugang,
Wang Jun,
Song Zhenshun,
Chen Caiping,
Pan Yanglin,
Zhao Lina,
Sun Shiren,
Wu Kaichun,
Feitelson Mark A.,
Liu Jie,
Fan Daiming
Publication year - 2009
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20455
Subject(s) - hbx , celecoxib , apoptosis , biology , cancer research , cell growth , cell , cyclooxygenase , flow cytometry , cell cycle , transfection , microbiology and biotechnology , cell culture , pharmacology , biochemistry , enzyme , genetics
Hepatitis B virus (HBV) X protein (HBx) and cyclooxygenase‐2 (COX‐2) are all playing roles in hepatocellular carcinoma (HCC), but the reversing effects of COX‐2 inhibitors on the neoplastic features caused by HBx protein is still unclear. To further evaluate the therapeutic potential of celecoxib on HBx mediated transformation, HCC cells transfected with HBx gene were treated with COX‐2 selective inhibitor, celecoxib. The amount the main metabolite of COX‐2, prostaglandin E2 (PGE2), was determined by using high sensitivity ELISA. Electron microscope and flow cytometry was used to analyze cell apoptosis and cell cycle distribution. RT‐PCR and Western blot were used to identify the molecules involved in celecoxib induced cell apoptosis. The results showed that celecoxib inhibited cell growth more significantly and also induced more cell apoptosis in HBx over‐expression cells than in control cells. Celecoxib could selectively inhibited COX‐2 expression and PGE2 production. Celecoxib also inhibited p 473Ser Akt, raf and p53 expression, and induced apoptosis by release of cytochrome c and activation of caspase 9, 3, and 6, which were more remarkably in HBx positive cells than in control cells. These results suggest that celecoxib had potent cell growth inhibitory effects on HBx positive HCC cells mainly through inducing more cell apoptosis, and these findings provide a new insight into the anticancer effects of celecoxib against HBx related HCC. © 2008 Wiley‐Liss, Inc.