Inhibitory effect of rapamycin on proliferation of H_(22) hepatic cancer in mice / 西安交通大学学报(医学版)

ABSTRACT

Objective To explore rapamycin's inhibitory effect on proliferation of H_(22) hepatic cancer in mice. Methods In vitro study H_(22) hepatic cancer cell lines were cultured with rapamycin, CsA, FK506, and proliferation was determined through MTT. The influences of different agents on the H_(22) hepatic cancer cell cycle were observed by flow cytometry. The vascular endothelial growth factor (VEGF) concentration of the supernatant fluid of the cultured H_(22) hepatic cancer cell was detected by ELISA. In vivo study C57BL/6 to Balb/c mice allogenic skin transplant was established, and the H_(22) hepatic cancer cell was implanted under skin. Rapamycin, CsA, FK506 and 5-FU were fed to the mice, respectively. The effect of different immunosuppressors on the survival of skin graft was observed while the proliferation of the transplant tumor was investigated. VEGF concentration of treated mice serum was examined by ELISA. The microvessel density of the transplanted tumor was observed through immunohistochemistry staining of CD34. Results The proliferation of the H_(22) hepatic cancer cells was inhibited by rapamycin at the concentration different dose of rapamycin, the VEGF concentration of the supernatant fluid decreased significantly (P<0.05). The number of S phase cells decreased significantly compared to that of other agents (P<0.05). When rapamycin, the lengthened survival time of the skin grafts was similar to that in CsA and FK506 groups. But the tumor volume was smaller than that in CsA and FK506 groups (P<0.05). Compared to that in the control group, the VEGF concentration of mice serum decreased in rapamycin group (P<0.05), and the microvessel density of the transplant tumor was reduced greatly (P<0.05). Conclusion Rapamycin, as an immunosuppressor, significantly resists immunologic rejection and inhibits the proliferation of H_(22) hepatic cancer, thus having its advantage in treating malignant hepatic cancer with liver transplantation.