Abstract: Objective To investigate antiproliferative effect and reduction of VEGF expression of rapamycin on ADPKD cystic lining epithelial cells. Methods ADPKD cystic lining immortalized epithelial cells(WT9-12) were stimulated by rapamycin with different concentrations. After treatment, MTT method was performed to detect the levels of proliferation, the mRNA expressions of VEGF were measured by Real-time PCR. Western blot method was used to detect the protein expressions of cyclinD, P21, Bcl2, Bax and VEGF. Results Rapamycin , a mTOR inhibitor, was found to induce cell growth inhibition, apoptosis as well as a stable accumulation of cells in the G0/G1 phase. Western blot of cultured WT9-12 cells demonstrated that Rapamycin downregulated cyclinD, Bcl2 and upregulated p21, Bax expressions. In addition, realtime-PCR detected elevated levels of VEGF mRNA in primary cells from ADPKD patients and WT9-12 cells compared with normal tubule cells. Rapamycin downregulated VEGF expression in WT9-12 cells. Conclusion Rapamycin induces ADPKD cystic lining epithelial cells growth inhibition, apoptosis and inhibits VEGF expression, which may be one of mechanisms of rapamycin postponing ADPKD progression.

Key words: ADPKD, Rapamycin, Cell cycle, Apoptosis, VEGF