Abstract: Objective To investigat the effects of prohibitin1 (PHB1) on cell proliferation of human hepatocellular? carcinoma (HCC) cells, and to elucidate the mechanism of PHB1 in the occurrence and development of HCC.Methods HepG2 and SMMC-7721 cells were transfected with enhanced green fluorescent protein plasmid-PHB1 and PHB1-specific short hairpin ribonucleic acid (RNA) to induce the up-regulation and down-regulation of PHB1 expression. The cell proliferation, cell cycle and key regulators of cell cycle were investigated by MTT assay, flow cytometry, real-time polymerase chain reaction and western blot. Results Overexpression of PHB1 arrested the HepG2 and SMMC-7721 cell cycle in G0/G1 phase (67.28%±2.94 vs 56.71% ± 2.56, t=6.64, P=0.00; 69.48%±3.82 vs 60.43%±2.59, t=4.80, P=0.00), decreased the proportion of cells in S phase (14.74%±1.45 vs 24.13%±1.92, t=9.54, P=0.00; 13.73%±1.26 vs 25.50% ± 2.30, t=10.99, P=0.00), and inhibited cell proliferation. Furthermore, as PHB1 overexpressed, the messenger RNA and protein levels of p53 and p21CIP1 were increased, while those of cyclin A2, cyclin E1 and cyclin-dependent kinase 2 were decreased in the HepG2 and SMMC-7721cells (P<0.01). Conversely, these results were reversed when the expression of PHB1 was inhibited.Conclusion Overexpression of PHB1 arrested the HCC cell cycle in G0/G1 phase, thus inhibit cell proliferation, which might be related to p53-mediated G0/G1 phase-related cell cycle protein.

Key words: Prohibitin1, Hepatocellular carcinoma cells, Cell proliferation, Cell cycle