二甲双胍对结肠癌细胞增殖、周期及凋亡的影响

  目的 研究二甲双胍对人结肠癌细胞株SW480增殖、周期及凋亡的影响，并初步探讨其可能的机制。方法 体外培养人结肠癌细胞株SW480，给予不同浓度二甲双胍干预，MTT法检测细胞增殖情况，流式细胞仪检测细胞周期及凋亡，Real time-PCR法检测相关基因mRNA的表达。结果 二甲双胍可以抑制SW480细胞的增殖，并呈时间-剂量依赖性。20mmol/L二甲双胍干预48h后与对照组相比，细胞G0/G1期比例升高，S及G2/M期比例均降低；细胞凋亡比率增高；Real time-PCR示周期相关基因CyclinD1 mRNA表达明显下调（P0.05)，凋亡相关基因BCL-2 mRNA表达明显下调，CASP3及BAX mRNA 表达明显上调(P<0.01)。结论 二甲双胍能够抑制人结肠癌细胞株SW480的增殖，G0/G1期细胞周期阻滞，促进细胞凋亡；其机制可能与上调及下调某些周期、凋亡相关基因的mRNA表达有关。

Effects of Metformin on Proliferation,Cell Cycle and Apoptosis in Colon Carcinoma Cell

Objective To observe the effect of metformin on the proliferation,cell cycle and apoptosis in human colon cancer cell line SW480 and study the possible mechanism.Methods The proliferation of SW480 cells treated with different concentrations of metformin was assessed by MTT assay,and the cell cycle and apoptosis changes were analyzed by flow cytometry.The expression of related genes mRNA were determined by Real-time PCR.Results Metformin decreased the proliferation of SW480 cells in a dose-and time-dependent manner.Compared with the control group,metformin-treated(20 mmol/L,48 h)cells were accumulated at G0/G1 stage.Cells at S and G2/M stage were decreased.The rates of apoptotic cells were increased.The expressions of CyclinD1 and BCL-2 mRNA were down-regulated(P <0.01),while the expressions of CASP3 and BAX mRNA were up-regulated(P < 0.01).No significant difference in P27 expression(P > 0.05) was observed.Conclusion Metformin can inhibit the growth and block the cell cycle at G0/G1 stage of SW480 cells,and induce apoptosis mainly by down-regulating CyclinD1,BCL-2 mRNA and up-regulating CASP3,BAX mRNA.