ST2325对erbB2过表达的乳腺癌细胞周期的影响及分子机制  

Effect of ST2325 on cell cycle in erbB2-overexpressing breast cancer MDA-MB-453m1 cells and its mechanism

作　　者：朱孝峰[1] 曾益新[1] 杨大俊 

机构地区：[1]中山医科大学肿瘤防治中心肿瘤研究所,广东广州510060 [2]美国乔治城大学Lombardi癌症中心,美国华盛顿特区20007

出　　处：《中国癌症杂志》2001年第2期97-100,共4页China Oncology

基　　金：国家自然科学基金 (No.3990 0 183);中山医科大学"211工程"肿瘤学重点学科基金 (No .980 6 9)资助

摘　　要：目的 :我们已证明ST2 32 5对erbB2受体酪氨酸激酶有明显的抑制作用 ,本实验研究ST2 32 5对erbB2过表达的乳腺癌MDA MB 45 3m1细胞周期分布的影响及分子机制。方法 :流式细胞术检测细胞周期的分布 ;Westernblot法检测蛋白表达量的变化。结果 :ST2 32 5处理MDA MB 45 3m1细胞 2 4小时后 ,流式细胞仪分析可见在 0、6 2 5、12 5、2 5 0、5 0 0、10 0 μmol L浓度下 ,MDA MB 45 3m1细胞G0 G1期分别为 :48 6 2 %、48 83%、49 5 9%、5 2 18%、6 1 0 0 %、83 96 % ;S期分别为 33 34 %、33 16 %、32 78%、30 77%、2 5 6 2 %、7 0 8% ;G2 M期分别为 :18 0 4%、18 0 1%、17 6 3%、17 0 5 %、13 38%、8 96 %。用不同浓度的ST2 32 5处理MDA MB 45 3m1细胞 2 4小时后 ,Westernblot法检测呈现ST2 32 5处理后 ,细胞中p2 7上调 ,Rb的高磷酸化状态下降 ,CyclinD1蛋白水平下降。ST2 32 5对MAPK和AKT的激活有明显的抑制作用。结论 :ST2 32 5能诱导erbB2过表达的乳腺癌MDA MB 45 3ml细胞停止于G1期 ,且与P2 7上调、Rb的高磷酸化状态下降、CyclinD1蛋白水平下降有关。Purpose:Effect of ST2325 on cell cycle in erbB2-overexpressing MDA-MB-453m1 cells and its mechanism was investigated.Methods:Cell cycle distribution was examined using flow cytometry. The protein expression was detected with Western blot analysis.Results:Under concentrations of 0,6.25,12.5,25.0,50.0,100 μmol/L,the percentrages of G0/G 1 in MDA-MB-453m1 were 48.62%, 48.83%, 49.59%, 52.18%, 61.0%,83.96%; the percentages of S were 33.34%, 33.16%, 32.78%,30.77%,25.62%,7.08%;the percentages of G 2M were 18.04%, 18.01%,17.63%,17.05%, 13.38%, 8.96%. After MDA-MB-453m1 cells were treated with different concentrations of ST2325 for 24 hours, Western blot assay showed up-regulation of p27 protein expression and decrease of hyperphosphorylated Rb and cyclin D1 protein expression .Activation of MAPK and AKT in MDA-MB-453m1 was markedly inhibited by ST2325.Conclusions:ST2325 induces G1 arrest in erbB2-overexpressing MDA-MB-453m1 cancer cells. G1 arrest is associated with p27 upregulation,decrease of cyclinD1 protein and hyperphosphorylated Rb.

关 键 词：乳腺肿瘤 ST2325 ERBB2 细胞周期 基因过表达 

分 类 号：R737.9[医药卫生—肿瘤]