二甲双胍对三阴性乳腺癌细胞作用的实验研究  

Study of metformin on triple negative breast cancer cells

作　　者：刘杏娥[1] 孙晓东[2] 

机构地区：[1]浙江医院肿瘤内科,浙江杭州310013 [2]浙江大学医学院附属邵逸夫医院普外科

出　　处：《全科医学临床与教育》2011年第6期609-612,共4页Clinical Education of General Practice

摘　　要：目的探讨二甲双胍对三阴性乳腺癌的作用及可能机制。方法不同浓度的二甲双胍作用三阴性乳腺癌细胞MDA-MB-231后,采用MTT法检测细胞增殖,流式细胞仪检测细胞凋亡,Western blot技术检测ERK1/2、pERK1/2的表达水平,将肿瘤细胞接种裸鼠后给予二甲双胍治疗,观察肿瘤组织的抑瘤率。结果不同浓度的二甲双胍与乳腺癌MDA-MB-231细胞共培养后,随着二甲双胍浓度的逐渐增加,MDA-MB-231细胞的增殖抑制也逐渐增加。经统计学分析发现,二甲双胍20mM组与对照组比较;二甲双胍30mM组与20mM组、对照组比较;二甲双胍40mM组与30mM组、20mM组、对照组比较;二甲双胍50mM组与40mM组、30mM组、20mM组、对照组比较,差异均有统计学意义(t分别=16.04;4.36、29.24;21.33、23.46、40.61;3.70、31.80、33.16、64.17,P均<0.05)。乳腺癌MDA-MB-231细胞经二甲双胍处理后,细胞凋亡率(27.31%)明显高于对照组(2.36%),两者比较,差异有统计学意义(t=29.93,P<0.05)。经二甲双胍处理的MDA-MB-231细胞,其ERK1/2的磷酸化水平降低。将乳腺癌MDA-MB-231细胞接种于裸鼠,经二甲双胍治疗后,肿瘤组织的抑瘤率明显高于对照组,两者比较,差异有统计学意义(t=37.63,P<0.05)。结论二甲双胍对三阴性乳腺癌细胞有抑制作用,其机制可能是抑制EGFR信号通路的分子活化。Objective To investigate the effects of metformin on triple negative breast cancer cells and the possible molecular mechanisms.Methods The triple negative breast cancer cells MDA-MB-231 were treated with metformin,Growth inhibition ratio of the cells were measured by MTT assay,apoptosis were detected by flow cytometery,the expressive level of ERK1/2,pERK1/2 were detected by Western blot.The nude mice,challenged with MDA-MB-231 cells,were treated with metformin,tumor growth control were observed.Results Breast cancer cells MDA-MB-231 were cocultured with different concentration＇s metformin,the increased growth inhibition rates of the cells were correlated with the increased concentration of metformin.The growth inhibition rates of metformin（20 mM）group is significantly different with that of the control group;the growth inhibition rates of metformin（30 mM）group was significantly different with that of metformin（20 mM）group and control group;the growth inhibition rates of metformin（40 mM）group was significantly different with that of metformin（30 mM,20 mM）groups and the control group;the growth inhibition rates of metformin（50 mM）group was significantly different with that of metformin（40 mM,30 mM,20 mM）groups and the control group（t =16.04,4.36,29.24,21.33,23.46,40.61,3.70,31.80,33.16,64.17,P0.05）.Apoptosis of the metformin treated group（27.31%） were significantly different with that of the control group（2.36%）（t =29.93,P0.05）.The expressive level of pERK1/2 in metformin treated group were lower than that in the control group.The tumor growth control of nude mice after metformin treated were significantly different with that of the control group（t =37.63,P0.05）.Conclusions Metformin can inhibit the proliferation in triple negative breast cancer cells.The inhibition of EGFR signaling pathway is the possible underlying molecular mechanism.

关 键 词：二甲双胍 乳腺癌 三阴性 

分 类 号：R737.9[医药卫生—肿瘤]