Antiproliferative and Overadditive Effects of Rapamycin and FTY720 in Pancreatic Cancer Cells In Vitro

Abstract

Rapamycin inhibits the growth of several tumors including pancreatic carcinoma both in vitro and in vivo. The antitumor effects of FTY720 were also shown recently. The present study was performed to investigate the in vitro antiproliferative capacity of combined treatment with rapamycin and FTY720 on pancreatic cacinoma cell lines. Materials and Methods The Panc-1 and AsPc-1 cell lines were employed as the pancreatic carcinoma model in vitro. For monotreatment experiments, rapamycin was added in increasing doses from 0.002 μmol/L to 200 μmol/L; FTY720 was used from 1 μmol/L to 15 μmol/L. For combined treatment, two concentrations of rapamycin were combined with seven concentrations of FTY720; or two concentrations of FTY720 with five concentrations of rapamycin. The antiproliferative capacity was assessed by the MTT assay. Results Rapamycin and FTY720 inhibited MTT incorporation into Panc-1 and AsPc-1 in dose-dependent fashion with or without serum stimulation. In coincubation experiments, great susceptibility to rapamycin was seen when combined with 10 μmol/L FTY720. An effective combination for AsPc-1 was 10 μmol/L FTY720 with 0.002 μmol/L rapamycin, resulting in more than 50% inhibition of MTT incorporation, and for Panc-1, 10 μmol/L FTY720 with 0.002 μmol/L rapamycin and 10 μmol/L FTY720 with 20 μmol/L rapamycin; the corresponding inhibition levels reached about 40% and 60%, respectively. Conclusion Rapamycin and FTY720 showed dose-dependent antiproliferative effects on pancreatic carcinoma cell lines in vitro both alone and in combination. The combined use of rapamycin and FTY720 showed additive and supra-additive antiproliferative effects on pancreatic carcinoma cell lines. The susceptibility of pancreatic carcinoma cells to rapamycin was significantly enhanced when combined with FTY720.