HSP90抑制剂17-DMAG影响结肠癌SW620细胞生长的实验研究  

Effects of HSP90 inhibitor 17-DMAG on the colon cancer cell line SW620:an experimental study

作　　者：邬叶锋[1] 马芳[2] 张丽军[2] 汤建燕[1] 赵登秋[1] 

机构地区：[1]上海市第六人民医院金山分院普外科,201599 [2]上海市公共卫生临床中心科学研究部

出　　处：《中华临床医师杂志（电子版）》2012年第24期8046-8050,共5页Chinese Journal of Clinicians(Electronic Edition)

基　　金：上海市金山区卫生局科研基金(2011-12)

摘　　要：目的研究热休克蛋白90(HSP90)新型抑制剂17-DMAG对结肠癌细胞株SW620增殖及凋亡的影响,并对其机制作初步探讨。方法以不同浓度的17-DMAG作用于对数生长期的结肠癌SW620细胞,显微镜下观察细胞凋亡形态学变化;应用CCK8法检测其吸光度值,并计算细胞生长抑制率;以Annexin V-FITC和PI双染法检测各组细胞凋亡率的变化;采用流式细胞仪分析各组细胞的细胞周期变化。结果光学显微镜观察到17-DMAG药物处理组的细胞出现细胞凋亡现象。CCK8法显示17-DMAG对结肠癌SW620细胞株的生长增殖有抑制作用,并呈时间-剂量依赖性(P<0.05)。Annexin-FITC/PI双染色法检测结果显示17-DMAG浓度为1.0μmol/L、2.5μmol/L、5.0μmol/L的细胞凋亡率分别为30.03%、50.50%和77.23%,与对照组相比有统计学差异(P<0.05)。流式细胞仪细胞周期分析显示,经17-DMAG药物处理过的不同浓度的药物组与对照组比较,G0/G1期细胞比例显著上升,S期细胞比例下降,G2/M期细胞比例显著上升,有统计学差异(P<0.05);但各浓度17-DMAG药物组间比较,G0/G1期、S期、G2/M期细胞比例无明显变化,差异无统计学意义(P>0.05)。结论 HSP90抑制剂17-DMAG对结肠癌细胞SW620的生长增殖有明显的抑制作用,呈时间和剂量依赖性,并诱导其凋亡;同时,17-DMAG影响SW620细胞的周期,但这种影响与17-DMAG的浓度无关。Objective To investigate effects of HSP90 novel inhibitor 17-DMAG on the proliferation and apoptosis of human colon cancer cell line SW620 and explore its mechanism.Methods With different concentrations of 17-DMAG on growth period of the human colon cancer cell line SW620,apoptotic morphological changes were observed under microscope;CCK8 method was applicated to detect the absorbance values,and the cell growth inhibition rate were calculated;flow cytometric was used to analyse the cell cycle changes of each group;Annexin V-FITC and PI double staining method were used for detecting clusters of apoptotic cells rate of change.Results We observed through microscope that 17-DMAG drug treatment group cells appeared apoptosis.CCK8 assay suggested that 17-DMAG inhibited the proliferation of colon cancer cell line SW620 in a dose-and time-dependent manner(P<0.05).Annexin-FITC/PI assay revealed that cell apoptotic ratios of 1.0 μmol/L,2.5 μmol/L,5.0 μmol/L concentrations were 30.03%,50.50% and 77.23%,the difference was significant compared to the control group(P<0.05).The cell cycle analysis by FCM showed that the 17-DMAG groups treated with different concentrations of the drug compared with the control group,the G0/G1 cell ratio increased significantly,S cell ratio decreased,G2/M cell ratio increased significantly,with statistical difference(P<0.05);but the concentration of 17-DMAG drug groups comparison of G0/G1,S,G2/M period,the cell ratio did not change significantly,the differences were not statistically significant(P>0.05).Conclusions HSP90 inhibitor 17-DMAG can inhibit the proliferation of the human colon cancer cell line SW620 in a dose-and time-dependent,and induce its apoptosis.17-DMAG can effect the cell cycle of SW620 without dependence of the concentration of 17-DMAG.

关 键 词：结肠肿瘤 HSP90热休克蛋白质类 细胞增殖 细胞凋亡 17-DMAG 

分 类 号：R735.35[医药卫生—肿瘤]