法尼基转移酶抑制剂诱导小鼠胰岛素瘤胰岛β细胞凋亡的实验研究

Farnesyltransferase inhibitor R115777 induced apoptosis in murine insulinoma beta cells

目的探讨法尼基转移酶抑制剂对小鼠胰岛素瘤胰岛β细胞的抑制生长和诱导凋亡作用,为其作为抗肿瘤药物提供理论基础。方法体外培养小鼠胰岛素瘤胰岛β细胞Beta-TC-6,用不同稀释度的法尼基转移酶抑制剂R115777处理对数生长期的Beta-TC-6细胞,用MTT法观察不同浓度R115777对Beta-TC-6细胞增殖的抑制作用,用碘化丙啶染色荧光显微镜下观察R115777处理后Beta-TC-6细胞的形态学改变。用流式细胞术检测分析DNA含量直方图、亚G1期细胞所占百分比和细胞周期改变。结果R115777使小鼠胰岛素瘤胰岛β细胞Beta-TC-6的增殖受到明显抑制,并出现显著的凋亡现象,其作用与R115777的浓度成正相关。结论法尼基转移酶抑制剂R115777能抑制小鼠胰岛素瘤胰岛β细胞Beta-TC-6增殖,有必要作为一种可选的抗肿瘤药物而进一步研究。

Objective To explore the inhibition of growth and induction of apoptosis by Farnesyltransferase inhibitors in insulinoma beta cells of mice and to provide the theory basis for Farnesyltransferase inhibitors as the antitumor drugs.Methods Insulinoma beta cells Beta-TC-6 of mice are cultivated in vitro and are applied with different degrees of dilution of Farnesyltransferase inhibitors R115777.When the cells reach logarithm of growth period,MTT method was used in the observation of the inhibition of Beta-TC-6 cell proliferation by different concentration of R115777,propidium iodide staining fluorescence microscopy was utilized to observe Beta-TC-6 cell morphology changes after R115777 treatment,and flow cytometry was employed in the analysis of DNA content,G1 phase cell histogram percentage and the cell cycle changes.Results R115777 treatment resulted in significant inhibition of proliferation and significant apoptosis phenomenon in insulinoma beta cell Beta-TC-6 of mice and the action was positively correlated with the concentration of R115777.Conclusion Farnesyltransferase inhibitors R115777 can inhibit proliferation of insulinoma beta cell Beta-TC-6 of mice and can be considered as an optional antitumor drugs to carry out further research.