Effects Of All-trans Retinoic Acid On Human Liver Cancer Cell Line SMMC-7721

Objective The aim of this study was to observe inhibition effects and the induction of differentiation on the human liver cancer cell line SMMC-7721 in vitro after induced by all-trans retinoic acid(ATRA). At the same time, and expression change of Survivin was observed.Methods Human liver cancer cell line SMMC-7721 was treated by ATRA in 10-4,10-5,10-6,10-7,10-8mol/L respectively,and was detected at 24,48,72,96h.The effect of growth suppression was evaluated with MTT assay. Cell cycle,apoptosis rate were detected by flow cytometry(FCM) with PI staining or Annexin V/PI double stainings. The morphous change of SMMC-7721 cell were observed by invert microscope.Change of Survivin protein and mRNA expression level was examined by immunocytochemistry and RT-PCR.Resultsâ‘ After induced by ATRA, The cell proliferation was Significantly inhibited in time-dependent and dose-dependent manners,the tendency of inhibition increased along with the dose and time gradual increased;â‘¡After induced by ATRA, the apoptotic rates of SMMC-7721 cells were obvious, apoptotic rates increased along with the dose and time gradual increased. However, in the control group, the apoptotic rates were maintained low level;â‘¢After induced by ATRA, the cell cycle of SMMC-7721 cells was changed significently, G1/G0 phase cell proportion increased gradually, while the S phase decreased gradually, SMMC-7721 cells were accumulated in G0/G1 phase, but the influence to G2/M phase cell was small. The transformation from G0/G1 phase cells to S phase cells was blocked by ATRA. S phase cells reduced, G0/ G1 phase cells increased, the cell division cycle prolonged, division rates reduced, the cell proliferation was inhibited;â‘£The expression levels of Survivin decreased gradually compared with the chang of apoptotic rate and differentiation.Conclusions:â‘ ATRA inhibits the proliferation of human liver cancer cell line SMMC-7721 significantly;â‘¡The apoptosis in SMMC-7721 cells could be induced by ATRA;â‘¢The molecular mechanism of inducing apoptosis of SMMC-7721 may be related to down-regulation of Survivin transcription.