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目的:探讨二甲双胍对雌激素受体(ER)表达不同的乳腺癌细胞的作用效果差异,并初步研究相关分子机制。方法:药物干预细胞后,采用MTT检测细胞增殖、流式细胞术(FCM)检测细胞周期以及凋亡、RT-PCR检测细胞HIF-1α的mRNA转录水平。结果:药物干预细胞后,各组细胞增殖均受到药物的抑制作用,且随药物浓度以及作用时间的增加而增强(P<0.05)。其中二甲双胍对于MCF-7(ER+)细胞的抑制率在各浓度组均高于MDA-MB-231(ER-)细胞(P<0.05)。FCM检测提示:二甲双胍对MCF-7(ER+)乳腺癌细胞G1期阻滞明显,且呈浓度依赖性增加(P<0.05)。但对于MDA-MB-231(ER-)细胞仅有20 mmol/L和40 mmol/L浓度组与对照组相比差异有显著性(P<0.05);且比同浓度组MCF-7(ER+)细胞G1期的阻滞百分比低(P<0.05)。二甲双胍对于两种乳腺癌细胞的凋亡作用不明显(P>0.05)。RT-PCR检测HIF-1α的mRNA表达水平提示:两种乳腺癌细胞HIF-1α的mRNA表达水平均随药物浓度增加而减少(P<0.05)。结论:二甲双胍对ER阳性乳腺癌细胞的抑制作用优于ER阴性的乳腺癌细胞,可能与HIF-1α的低表达有关。
Objective: To investigate the effect of metformin on the expression of estrogen receptor (ER) in different breast cancer cells, and to study the underlying molecular mechanisms. Methods: Cell proliferation was detected by MTT assay. Cell cycle and apoptosis were detected by flow cytometry (FCM). The transcription level of HIF-1α mRNA was detected by RT-PCR. Results: After drug intervention, the cell proliferation in each group was inhibited by drugs, and increased with the increase of drug concentration and time (P <0.05). The inhibition rate of metformin on MCF-7 (ER +) cells in each concentration group was higher than that of MDA-MB-231 (ER-) cells (P <0.05). FCM showed that metformin had a significant G1 arrest in MCF-7 (ER +) breast cancer cells in a concentration-dependent manner (P <0.05). (P <0.05). However, compared with the control group, the concentration of MCF-7 (ER +) in MDA-MB- ) Cells had a lower percentage of arrest in the G1 phase (P <0.05). Metformin had no significant effect on the apoptosis of the two breast cancer cells (P> 0.05). The mRNA expression of HIF-1α by RT-PCR indicated that the mRNA expression of HIF-1α in both breast cancer cells decreased with the increase of the drug concentration (P <0.05). CONCLUSION: Metformin inhibits ER-positive breast cancer cells better than ER-negative breast cancer cells, which may be related to the low expression of HIF-1α.