Rapamycin Inhibit The Growth Of Hepatocellular Carcinoma In Nude Mice

Objective: IN the previous study we show that the new immunosuppressive drug rapamycin may reduce the risk of cancer development by infibition of the mTOR pathway while simultaneously providing effective immunosuppression. Our current study is to study the antitumor effect of rapamycin on hepatocellular carcinoma and the relevant mechanism.Methods: Nude mice bearing orthotopic xenografty human HCC were randomly divided into four groups: control, tacrolimus group,Rapamycin group, Rapamycin high dose group. The effect on the tumor growth was evaluated using tumor volume after 2 weeks. PCNA and VEGF expression of liver cancer tissue was detected with immunohistochemical stain. And the amount of VEGF mRNA in liver cancer tissue was detected with real-time RT-PCR.Results: The tumor volume was 310.15±40.16mm3, 605.59±116.23mm3, 99.19±15.27mm3, 151.61±27.81mm3 in control, Tacrolimus group,Rapamycin group and Rapamycin high dose group respectively. The tumor volume significantly decreased in Rapamycin group and Rapamycin high dose group but increased in tacrolimus group compare with control. PCNA and VEGF expression were downregulated in Rapamycin group and Rapamycin high dose group compare with control.Conclusion: The growth of HCC in the nude mice was inhibited when the animal were exposed to rapamycin but enhanced when exposed to tacrolimus. The antitumor effort of rapamycin attributes to the retardation of tumor cell growth and the downregulation of VEGF expression probably. Thus, the use of rapamycin may reduce the chance of recurrent cancer in high-risk liver transplant patient.