Effect of low-dose rapamycin on tumor growth in two human hepatocellular cancer cell lines.

ABSTRACT

AIM: Liver transplantation is the best treatment for patients with early hepatocellular carcinoma (HCC) and cirrhosis. A limiting factor for long-term survival remains posttransplant tumor recurrence. Thus, there is widespread discussion about the role of various immunosuppressive agents. The newly developed immunosuppressive drug rapamycin may aid to lower recurrence rates. We investigated the efficiency of rapamycin as compared with previous immunosuppressants in a tumor cell model. METHODS: We studied two HCC cell lines for cell-cycle and proliferation analyses after treatment with rapamycin or other immunosuppressants. To elucidate the underlying molecular signaling pathway, we performed Western blotting for phosphorylated p70 S6 kinase protein expression. RESULTS: Low-dose rapamycin inhibited tumor cell growth at doses of 1, 5, and 10 ng/mL, while standard immunosuppressants stimulated growth. A rapamycin dose of 20 ng/mL showed a marked decrease in the growth inhibition of both HCC cell lines compared to low-dose administration. CONCLUSION: Rapamycin in low doses inhibited the growth of two HCC cell lines in vitro. Inhibition of tumor cell growth was observed with a high dose of rapamycin (20 ng/mL), which appears to be the dividing line between growth and inhibition. We postulated that at higher doses the immunosuppressive effect of rapamycin is overrode by its antitumor effects.