AIM:To investigate the anti-tumor activity of ursolic acid(UA)and its derivatives isolated from Aralia decaisneanaon hepatocellular carcinoma both in vitro and in vivo.METHODS:In vivo cytotoxicity was first screened by3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide(MTT)assay.Morphological observation,DNAladder,flow cytometry analysis,Western blot and realtime PCR were employed to elucidate the cytotoxicmechanism of UA.Implanted mouse hepatoma H_(22)wasused to evaluate the growth inhibitory effect of UA invivo.RESULTS:UA could significantly inhibit the proliferationof HepG2 and its drug-resistance strain,R-HepG2 cells,but had no inhibitory effect on primarily cultured normalmouse hepatocytes whereas all the six derivativesof UA could not inhibit the growth of all tested celllines.Further study on mechanism demonstratedthat apoptosis and G_0/G_1 arrest were involved inthe cytotoxicity and cleavage of poly-(ADP-ribose)-polymerase(PARP).Downregulation of cyclooxygenase-2(COX-2)protein and upregulation of heat shock protein(HSP)105 mRNA correlated to the apoptosis of HepG2cells treated with UA.In addition,UA also could inhibitthe growth of H_(22)hepatoma in vivo.CONCLUSION:UA is a promising anti-tumor agent,butfurther work needs to be done to improve its solubility. AIM: To investigate the anti-tumor activity of ursolic acid (UA) and its derivatives isolated from Aralia decaisneanaon hepatocellular carcinoma both in vitro and in vivo. METHODS: In vivo cytotoxicity was first screened by 3- [4,5-dimethylthiazol- yl] -2,5-diphenyltetrazoliumbromide (MTT) assay. Morphological observation, DNAladder, flow cytometry analysis, Western blot and realtime PCR were employed to elucidate the cytotoxic mechanism of UA. Implanted mouse hepatoma H_ (22) was used to evaluate the growth inhibitory effect of UA invivo.RESULTS: UA could significantly inhibit the proliferation of HepG2 and its drug-resistance strain, R-HepG2 cells, but had no inhibitory effect of more cultured normal mouse hepatocytes but all the six derivatives of UA could not inhibit the growth of all tested celllines . Further study on the mechanism of apoptosis and G_0 / G_1 arrest were involved in the cytotoxicity and cleavage of poly- (ADP-ribose) -polymerase (PARP). Downregulation of cyclooxygenase-2 (COX- protein and upregulation of heat shock protein (HSP) 105 mRNA correlated to the apoptosis of HepG2 cells treated with UA. In addition, UA also could inhibit the growth of H 22 hepatoma in vivo. CONCLUSION: UA is a promising anti-tumor agent, butfurther work needs to be done to improve its solubility.