p38MAPK Signaling Pathway in Rosiglitazone-induced Apoptosis of Hepatocellular Carcinoma Cell Line HepG2

Objective To investigate the effects of Rosiglitazone (ROZ) on the proliferation and apoptosis of human hepatocellular carcinoma cell line HepG2 and to explore the role of p38MAPK signaling pathway in these processes. Methods HepG2 cell proliferation was determined by MTT method, and the apoptosis rates were measured by flow cytometry (FCM). The morphology of cell apoptosis was investigated by transmission electron microscopy (TEM). Western blot was performed to measure the protein expression related to p38MAPK signaling pathway. Result Rosiglitazone inhibited HepG2 cell proliferation in a concentration- and time-dependent manner (P<0.05), and the apoptosis rates were increased significantly (P<0.05). The typical morphological changes of apoptosis were chromatin condensation and aggregation at the periphery of nucleons and nuclear fragmentation. Rosiglitazone activated p-p38MAPK pathway, upregulated the expression of p-p53 and Bax, and down-regulated Bcl-2 expression in HepG2 cells (P<0.05), while with no effect on ERK1/2 phosphorylation. The rosiglitazone-induced apoptosis of HepG2 cells and the changes of p-p53, Bcl-2 and Bax proteins were partly blocked by p38MAPK inhibitor SB203580. Conclusion Rosiglitazone could activate p38MAPK pathway by inhibiting HepG2 cell proliferation and inducing its apoptosis. The mechanism may be related with p38MAPK signaling pathway regulating the expression of p-p53, Bcl-2 and Bax proteins.