辛伐他汀联合5-FU对K562细胞增殖及凋亡的影响

Effects of the combination of Simvastatin and 5-FU on proliferation and apoptosis of K562 cells

目的:探讨辛伐他汀(Sim)联合5-FU对白血病K562细胞增殖及凋亡的影响,探讨其作用机制。方法:体外培养人白血病K562细胞,用MTT法观察Sim联合5-FU对细胞的增殖抑制作用,实时荧光定量RT-PCR观察对bcr/abl融合基因mRNA表达水平的影响。流式细胞术、Hoechst33258染色观察Sim与5-FU联合应用诱导细胞凋亡的作用。结果:低浓度的Sim与5-FU联合应用在抑制细胞的增殖,诱导细胞凋亡,均较各单一高浓度用药组的作用明显增强,并且下调bcr/abl融合基因mRNA表达。结论:Sim与5-FU联用具有明显的协同抑制细胞增殖的作用,其作用机制可能与诱导细胞凋亡,下调bcr/abl融合基因的表达有关。

Aim：To study the effects of combination of simvastatin with 5-FU on K562 cells in vitro and their antitumor mechanisms. Methods： MTr assay was used to determine the inhibitory effects of the drugs on k562 cells and real time fluorescent quantitative reverse transcription-polymerase chain reaction （FQ-PCR） used to determine the mRNA levels of bcr/abl fusion gene. Apoptosis was analyzed by using flow eytometry and Hoechst33258 staining technique. Results： At lower concentrations,combination of simvastatin with 5-FU had greater inhibitory effects on growth and proliferation of the leukemia cells, and also induced apoptosis, when comparing with the higher concentrations of the drugs. It was found that all concentrations of the drugs used in this study showed to be able to suppress the expression of the fusion gene bcr/abl. Conclusion： Combination of simvastatin with 5-FU has a significantly synergie anti-cancer effect. The antitumor mechanism may be associated with induction of apoptosis and suppression of the fusion gene bcr/abl of K562 cells.