Effects of retinoic acid on human hepatocarcinoma cell lines apoptosis

Objective To investgate the growth inhibition and apoptosis induced by all-trans-retinoic acid (ATRA), and its possible molecular mechanism in human hepatocarcinoma cell lines. Methods Human hepatocarcinoma cell lines SMMC-7721 were cultured with ATRA at the concentration of 0.5μg/ml for 4 days. The cells apoptosis and growth inhibition were assessed by cytomorphology and counting the number of cells to calculate the rate of growth-inhibited. Cell cycle, tumor associated genes p53, Fas and Bcl-2 were analyzed with flow cytometry.Results ATRA inhibited the growth of hepatocarcinoma cells SMMC-7721 in vitro. Apoptosis cells of total cells were 16% compared with control 6.9% (P0.01) and a sub-G 1 phase cell peak was observed. Morphological observation with light microscope revealed apoptosis feature, i.e. chromatin condensation, nucleus fragmentation and cytoplasmic blebbing. There was a significant different rate of growth-inhibited between the two groups.(P0.005). The expression of p53 and Fas were up-regulated, and Bcl-2 was down-regulated when treated with ATRA in contrast to control.Conclusion ATRA can induce human hepatocarcinoma cell apoptosis. It could be a potential therapeutic agent for hepatocarcinoma. Tumor associated genes such as p53, Fas and Bcl-2 may be involved in molecular mechanism of ATRA effects.