A farnesyl transferase inhibitor induces apoptosis of insulinoma pancreatic β cells of mouse

Abstract

This study is to investigate the effect of a Farnesyl Transferase Inhibitor (FTI) R115777 on apoptosis of mouse insulinoma pancreatic β cells. MTT assay was used to investigate the proliferative inhibition of in vitro cultured mouse insulinoma pancreatic β cell lines by a FTI R115777. The morphological changes of the cells were observed using a fluorescence microscope by staining with Hoechst 33258 and propidium iodide after the treatment with FTI R115777. The apoptosis rate of R115777-treated beta-TC-6 cells was detected by flow cytometry. The expressions of caspase-3 and caspase-9 of the R115777-treated beta- TC-6 cells were assayed by spectrophotometry. In addition, the sub-cellular distribution of cytochrome c and the expressions of Bax and Bcl-2 proteins were detected by Western blot. After the treatment with FTI R115777, the proliferation of the mouse insulinoma pancreatic β cell lines was significantly inhibited. Significant apoptosis was observed in the treated beta-TC-6 cells. The effect of R115777 on the apoptosis of beta-TC-6 cells showed time- and dose-dependent manners. The expressions of caspase-3, caspase-9 and Bax in the R115777-treated beta-TC-6 cells increased, while the expression of Bcl-2 decreased. The sub-cellular distribution of cytochrome-c changed, with reduced cytochrome-c in mitochondria and increased cytochrome-c in cytoplasm. FTI R115777 can inhibit the proliferation of mouse insulinoma pancreatic β cell lines, and might induce cell apoptosis through the mitochondrionmediated pathway. R115777 could be further studied as a potential antitumor drug.