桔梗皂甙D对人胃癌细胞SGC7901增殖的抑制作用和机制研究  

Inhibitory Effect of Platycodin D on Proliferation of SGC7901 Cells and Moleclar Mechanism

作　　者：代群[1] 黄宣[1] 陈喆[1] DAIQun HUANGXuan CHENZhe(First AffiliatedHospital of ghejiang Chinese Medical University, Hangzhou（310053)

机构地区：[1]浙江中医药大学附属第一医院,杭州310006

出　　处：《浙江中医药大学学报》2017年第7期573-579,共7页Journal of Zhejiang Chinese Medical University

基　　金：国家自然科学基金项目(81673745)~~

摘　　要：[目的]探讨桔梗皂甙D(platycodin D,PD)对人胃癌细胞株SGC7901增殖的抑制作用及作用机制。[方法]体外培养人胃癌细胞株SGC7901,加入终浓度分别为5~20μm·L-1的PD。采用MTT法测定药物对细胞增殖的抑制作用,Annexin V/PI双标法检测细胞凋亡率,JC-1检测线粒体膜电位的变化,Western blot检测PD对凋亡相关蛋白cleaved caspase-3、cleaved caspase-9、cleaved PARP、bcl-2、bax和对MAPK信号通路蛋白ERK、JNK、p38及其磷酸化蛋白p-ERK、p-JNK、p-p38表达的影响。[结果]MTT结果显示,PD作用24h和48h后,PD对SGC7901细胞增殖的抑制随浓度的增加而增强;PD作用SGC7901后,细胞凋亡率明显增加,线粒体膜电位降低。Western blot检测结果显示cleaved PARP、cleaved caspase-3、cleaved caspase-9、bax蛋白表达量随着药物浓度的增加而升高,bcl-2蛋白表达下降,同时p-JNK、p-p38水平明显升高,p-ERK蛋白水平下降,ERK、JNK、p38蛋白的表达无明显变化。[结论]PD对胃癌细胞SGC7901有抑制增殖和诱导凋亡的作用。PD通过抑制ERK信号通路从而抑制细胞增殖,通过激活JNK和p38信号途径调控bax和bcl-2表达,导致线粒体膜电位下降,进而激活caspase,诱导癌细胞凋亡的发生。[Objective] To investigate the effects of platycodin D（PD） on the proliferation and apoptosis of human stomach cancer SGC7901 and the related mechanism. [Methods] SGC7901 was cultured in virto and was treated with 5~20μm·L-1concentrations of PD. Cell proliferation was examined by MTT assay.Cell apoptosis was detected by Annexin V FITC/PI double staining. The change of mitochondrial trans-membrane potential was measured by JC-1 staining.The potein expression of cleaved caspase-3, cleaved caspase-9, cleaved PARP, bcl-2, bax, p-ERK, ERK, p-JNK, JNK, p-p38 and p38 detected by Western blot. [Results] MTT results showed that PD inhibited the growth of SGC7901 cells in a dose-dependent manner at 24 h and 48 h. SGC7901 cells treated with PD for 24 h showed significantly enhanced apoptosis and weakened mitochondrial membrane potential compared with the control cells. Western blot results showed that PD could up-regulate expression of cleaved PARP, cleaved caspase-3, cleaved caspase-9, bax, p-JNK, p-p38 protein, decreased bcl-2,p-ERK protein, the expression of ERK, JNK, p38 protein did not change significantly. [Conclusion] PD may inhibit the proliferation and induce the apoptosis of SGC7901 cells. These findings indicated that PD inhibited cell proliferation by inhibiting the ERK signaling. PD effect on bax and bcl-2 by activation of JNK and p38 signaling pathway resulted in the decrease of mitochondrial membrane potential and activation of caspase, which induced the apoptosis of cancer cells.

关 键 词：PD SGC7901 细胞凋亡 线粒体膜电位 BCL-2家族蛋白 MAPK信号通路 

分 类 号：R331[医药卫生—人体生理学]