摘要
Arsenic trioxide (As2O3), an effective agent against acute promyelocytic leukemia, has been reported to inhibit the viability of solid tumors cell lines recently. The detailed molecular mechanism underlying the As2O3-induced inactivation of the cdc2 and possible functional role of PTEN in the observed G2/M arrest has yet to be elucidated. Here, we assessed the role of PTEN in regulation of As2O3-mediated G2/M cell cycle arrest in Hepatocellular carcinoma cell lines (HepG2 and SMMC7721). After 24?h following treatment, As2O3 induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. The sustained G2/M arrest by As2O3 is associated with decreased cdc2 protein and increased phospho-cdc2(Tyr15). As2O3 treatment increased Wee1 levels and decreased phospho-Wee1(642). Moreover, As2O3 substantially decreased the Ser473 and Thr308 phosphorylation of Akt and upregulated PTEN expression. Downregulation of PTEN by siRNA in As2O3-treated cells increased phospho-Wee1(Ser642) while decreased phospho-cdc2(Tyr15), resulting in decreased the G2/M cell cycle arrest. Therefore, induction of G2/M cell cycle arrest by As2O3 involved upregulation of PTEN. J. Cell. Biochem. 113: 35283535, 2012.
- 出版日期2012-11
- 单位哈尔滨医科大学