Abstract: Objective To investigate the effects of oleanolic acid on the growth of human liver cancer HCCLM3 cells transplanted tumor in nude mice, the apoptosis of tumor tissues and the expression of related genes. Methods Human liver cancer HCCLM3 cells were inoculated into the subcutaneous skin of BALB/c nude mice to construct liver cancer transplantation tumor model, and the nude mice were randomly divided into model group and drug group, which were given 0.01 mL/g corn oil and 5 mg/kg oleanolic acid by gavage, respectively. The general state, body weight, tumor weight and volume of nude mice in each group were measured and recorded during administration. The pathological changes of cell necrosis, cell proliferation and apoptosis in transplanted tumor tissues were detected by HE, Ki67 and TUNEL staining, respectively. The mRNA expression levels of CyclinD1, CyclinE1, CDK4, Bcl⁃2 and Bax genes in transplanted tumor tissues were detected by qRT⁃PCR. Results Compared with the model group, there was no significant effect on the body weight of nude mice in the drug group, while the weight and volume of transplanted tumor were significantly decreased (all P<0.05). HE staining showed that the morphology of transplanted tumor in the drug group changed significantly, and necrotic areas appeared. The positive expression intensity of Ki67 in tumor tissues of the drug group was significantly lower than that of the model group (P<0.01); the positive expression intensity of  TUNEL was significantly higher than that of the model group (P<0.05).The mRNA expression levels of proliferation⁃related genes CyclinD1, CyclinE1 and CDK4 in transplanted tumor tissues were decreased after oleanolic acid administration, but the differences were not statistically significant (all P>0.05); the mRNA expression level of anti⁃apoptosis⁃related gene Bcl⁃2 was decreased (P<0.05), while the mRNA expression level of pro⁃apoptosis⁃related gene Bax was increased (P<0.01). Conclusions Oleanolic acid can inhibit the growth of human liver cancer HCCLM3 cells transplanted tumors in nude mice, and its mechanism may be related to the inhibition of cell proliferation and the induction of apoptosis.

Key words: Liver cancer, Oleanolic acid, Transplanted tumor, Proliferation, Apoptosis