芹菜素与丹参酮ⅡA的协同抗肿瘤作用及机制

被引:6
作者
李莹雪 [1 ,2 ]
王锐银 [2 ]
包永明 [1 ]
机构
[1] 大连理工大学生物工程学院
[2] 广州神农生物技术有限公司神农中药研究所
关键词
丹参酮ⅡA; 芹菜素; 协同作用; 抗肿瘤; 细胞凋亡; 细胞周期阻滞;
D O I
暂无
中图分类号
R285 [中药药理学];
学科分类号
100806 [中药药理学];
摘要
目的研究芹菜素(Api)和丹参酮ⅡA(TanⅡA)联用对多种肿瘤细胞的协同抗肿瘤作用,并揭示其发生协同作用的机制。方法以人胃癌BGC823细胞、人乳腺癌MCF7细胞、人肝癌SMMC7721细胞为研究对象,采用MTT法检测Api和TanⅡA联用对细胞的增殖抑制作用;采用AV-PI双染法、PI染色法检测药物对BGC823细胞凋亡、细胞周期的影响;免疫印迹法检测BGC823细胞凋亡相关蛋白p53、BAX/BCL-2和周期蛋白B1、D1的表达;圆二色和DNA熔点法检测药物与DNA结合情况;S180荷瘤鼠模型检测药物的抑瘤效果。结果 Api与TanⅡA联用对BGC823等肿瘤细胞的增殖有协同抑制作用,联用指数CI在0.28左右。两药联用显著增加了细胞凋亡(P<0.01),上调了胞内BAX/BCL-2比值(P<0.01);周期蛋白水平发生变化,细胞周期阻滞在S期得到强化。两药与DNA以两种不同方式结合,DNA热变性曲线显著改变。体内抑瘤实验证明与单药相比,两药联用荷瘤鼠肿瘤体积和肿瘤质量均显著降低(P<0.01),抑瘤效果与环磷酰胺相当,但不良反应较小。结论 Api与TanⅡA联用具有协同抗肿瘤作用;药物与DNA以不同的方式结合,加剧了细胞周期的阻滞,是二者产生协同作用的核心机制。
引用
收藏
页码:5788 / 5797
页数:10
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