姜黄素上调caspase-3和p53表达后对人肺癌干细胞增殖与侵袭的影响  

Effect of Curcumin on Suppressing Proliferation and Invasion of Human Lung Carcinoma-Initiating Cells via Up-Regulating Caspase-3 and P53

作　　者：赵雅瑞 张立凡[2] 刘特 

机构地区：[1]上海医药职工大学,上海200050 [2]复旦大学附属华东医院胸外科,上海200040 [3]上海中医老年医学研究所,上海200031

出　　处：《中国临床医学》2013年第3期259-262,共4页Chinese Journal of Clinical Medicine

基　　金：上海市科委医学引导基金项目(编号:10411967100)

摘　　要：目的:探讨姜黄素干预人肺癌干细胞caspase-3与p53后对肺癌细胞增殖和侵袭的影响。方法:采用流式细胞仪分选技术从肺癌细胞株A549中分选出CD44+/CD133+的肺癌干细胞(carcinoma-initiating cells,CICS);用四甲基偶氮唑蓝比色法检测不同浓度姜黄素对肺癌干细胞增殖的影响;用实时荧光定量聚合酶链反应和蛋白质印迹法检测肺癌干细胞系中caspase-3和p53的mRNA和蛋白水平;Transwell小室侵袭实验检测姜黄素对肺癌干细胞体外侵袭能力的影响。结果:姜黄素浓度增加至40μmol/mL后,姜黄素处理组的肺癌干细胞增殖抑制率大于阴性对照组和空白对照组(P<0.01),姜黄素对肺癌干细胞体外增殖抑制呈显著的剂量依赖性(IC50为61.06μmol/mL)。姜黄素处理组肺癌干细胞中caspase-3和p53基因mRNA的表达水平(3.64±0.59,4.98±0.82)高于阴性对照组(1.00±0.04,0.99±0.07)和空白对照组(0.99±0.07,1.03±0.27),差异有统计学意义(P均<0.01)。姜黄素处理组肺癌干细胞中caspase-3和P53蛋白表达水平(0.65±0.12,0.43±0.05)高于阴性对照组(0.05±0.02,0.08±0.03)和空白对照组(0.09±0.03,0.12±0.17),差异有统计学意义(P<0.01和0.05)。姜黄素处理组侵袭细胞数(26±15)少于阴性对照组(82±13)和空白对照组(78±12),差异有统计学意义(P<0.01)。结论:姜黄素能上调caspase-3及p53的表达,能显著抑制人肺癌干细胞在体外的增殖及侵袭。Objective：To investigate the effect of curcumin on expression of p53 and caspase-3 and its effects on the proliferation and invasion of human lung carcinoma-initiating cells（CICs）.Methods：The CD44＋/CD133＋ human lung CICs were sortted from the A549 human lung cancer cell line by flow cytometry（FCM）.The effect of different concentrations of curcumin on the proliferation of human lung CICs was detected by methyl thiazolyl tetrazolium（MTT） chromatometry.Real-time quantitative polymerase chain reaction（PCR） and Western blotting were used to detect the expression levels of mRNA and protein of p53 and caspase-3 in lung CICs after treating by curcumin.The transwell assay was used to detect the invasion of human lung CICs after treating by curcumin.Results： The proliferation inhibitory rate of human lung CICs in curcumin group was higher than those in negative control group and blank control group when curcumin concentration reached 40 μmol/mL（all P0.01）.Curcumin displayed a proliferation inhibitory effect on human lung CICs in a dose-dependent manner（the IC50 of curcumin was 61.06 μmol/mL）.The mRNA expression levels of caspase-3 and p53 in curcumin group（3.64±0.59,4.98±0.82） were higher（P0.01 and 0.05） than those in negative control group（1.00±0.04,0.99±0.07） and blank control group（0.99±0.07,1.03±0.27）.The protein expression of caspase-3 and p53 in curcumin group（0.65±0.12,0.43±0.05） were higher（P0.05） than those in negative control group（0.05±0.02,0.08±0.03） and blank control group（0.09±0.03,0.12±0.17）.The invasion cell amount of human lung CICs in curcumin group（26±15） was lower（P0.01） than those in negative control group（82±13） and blank control group（78±12）.Conclusions： Curcumin can suppress the proliferation and invasion of human CICs through up-regulating the expression of caspase-3 and p53.

关 键 词：姜黄素 肺癌干细胞 增殖 侵袭 CASPASE-3 P53 

分 类 号：R734.2[医药卫生—肿瘤]