飞燕草素对HER-2阳性乳腺癌的抑制效应及分子机制研究  

The inhibitory effect and molecular mechanism of delphindin on HER-2 positive breast cancer

作　　者：吴蔼林 韩彬[1] 彭佳媛 朱彦锋[1] 彭晓莉[1] 欧愚 余小平[1] WU Ai-lin;HAN Bin;PENG Jia-yuan;ZHU Yan-feng;PENG Xiao-li;OU Yu;YU Xiao-ping(Chengdu Medical College,Chengdu 610000,China)

机构地区：[1]成都医学院,610000

出　　处：《天津医药》2018年第9期910-915,共6页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(81573154;81773432)

摘　　要：目的探讨飞燕草素(Dp)对HER-2阳性乳腺癌的抑制效应及分子机制。方法以HER-2阳性乳腺癌细胞(MDA-MB-453和BT-474)为研究对象,经不同浓度Dp(10、20、40、80及160μmol/L)处理48 h,同等浓度的DMSO为溶剂对照(Control),采用CCK-8法检测Dp对细胞活性的影响,计算半数抑制浓度(IC50),以确定后续实验浓度;以不同浓度Dp(20、40及80μmol/L)处理细胞48 h,运用HE染色观察细胞形态学变化,流式细胞术检测细胞周期分布,原位细胞凋亡检测试剂盒(TUNEL)检测细胞凋亡率,采用Western blot检测NF-κB信号通路相关蛋白磷酸化水平。结果在10、20、40、80及160μmol/L浓度范围内,Dp能抑制MDA-MB-453和BT-474的增殖,IC50分别为41.02和60.97μmol/L;20、40及80μmol/L浓度范围内,与Control组相比,Dp处理组部分细胞脱落漂浮,裂解,细胞体积减小,G2/M期细胞比例增加,细胞凋亡率增加;与Control组相比,40及80μmol/L Dp处理组胞内p-NF-κB/p65、p-IκBα、p-IKKα/β、p-PKCα表达水平显著降低,IκBα、IKKα、IKKβ、PKCα表达水平增加(P<0.05)。结论 Dp通过阻断NF-κB信号通路,诱导MDA-MB-453、BT-474细胞G2/M期周期阻滞和凋亡,从而抑制乳腺癌增殖。Objective To investigate the inhibitory effect and molecular mechanism of delphinidin(Dp)on HER-2 positive breast cancer.Methods The HER-2 positive breast cancer cells(MDA-MB-453 and BT-474)were treated with different concentrations of delphinidin(10,20,40,80 and 160μmol/L)for 48 hours.The same concentration of DMSO was used as the solvent control.CCK-8 method was used to measure the effect of Dp on cell activity,and half maximal inhibitory concentration(IC50)was calculated to determine the concentration of subsequent experiments.The cells were treated with different concentrations of Dp(20,40 and 80μmol/L)for 48 hours.HE staining was used to observe the cell morphological changes.Flow cytometry was used to analyze the cell cycle.Cell apoptosis rate was detected by TUNEL assay.The phosphorylation levels of NF-κB signaling pathway related proteins were determined by Western blot assay.Results Delphinidin inhibited the proliferation of MDA-MB-453 and BT-474 in the concentration ranges of 10,20,40,80 and 160μmol/L(IC50:41.02 and 60.97μmol/L).In the concentrations of 20,40 and 80μmol/L,compared with the control group,it was found that some cells were detached,floated and lysed,and the cell volume was decreased,the proportion of cells in G2/M phase and the apoptosis rate were increased in DP treatment groups.Compared with the control group,the expression levels of p-NF-κB/p65,p-IκBα,p-IKKα/βand p-PKCαwere significantly decreased in the 40 and 80μmol/L Dp treatment groups,while the expression levels of IκBα,IKKα,IKKβand PKCαwere increased in the Dp treatment groups(P<0.05).Conclusion Delphinine can inhibit the proliferation of breast cancer cells by blocking the NF-κB signaling pathway and inducing the G2/M cycle arrest and apoptosis of MDA-MB-453 and BT-474 cells.

关 键 词：受体 表皮生长因子 抗肿瘤药 植物 乳腺肿瘤 细胞周期 飞燕草素 HER-2阳性乳腺癌 核因子-ΚB信号通路 

分 类 号：R737.9[医药卫生—肿瘤]