摘要
目的:探讨中药活性成分欧前胡素对肿瘤坏死因子相关凋亡诱导配体(TRAIL)的协同抗乳腺癌效应及分子机制。方法:将人乳腺癌细胞T-47D和MCF-7按对照组、欧前胡素组、TRAIL组、欧前胡素+TRAIL组及欧前胡素+TRAIL+死亡受体5(DR5)siRNA组进行分组,MTT法检测T-47D和MCF-7细胞活力,流式细胞术检测T-47D细胞凋亡和线粒体膜电位,Western blot实验和流式细胞术检测T-47D细胞表面DR5的表达水平及caspase-8、caspase-3的活化水平。结果:MTT实验结果显示,欧前胡素联合用药能显著提高各浓度TRAIL对T-47D和MCF-7细胞的杀伤活性;流式细胞术和Western blot结果显示欧前胡素处理能显著提高T-47D细胞DR5的表达水平和活性氧簇产生水平(P<0.05)。另外,流式细胞术和Western blot结果还显示,欧前胡素联合用药能显著增强TRAIL促进T-47D细胞线粒体膜电位损伤、caspase-8和caspase-3活化及凋亡的作用。结论:欧前胡素通过上调乳腺癌细胞DR5的表达水平发挥对TRAIL的协同抗乳腺癌效应。
AIM:To investigate the synergistic effect of imperatorin on enhancing the anti-tumor effect of TNF-related apoptosis-inducing ligand(TRAIL)on breast cancer and the mechanisms.METHODS:T-47D and MCF-7breast cancer cells were divided into control group,imperatorin group,TRAIL group,imperatorin+TRAIL group and imperatorin+TRAIL+death receptor5(DR5)siRNA group.The viability of T-47D and MCF-7cells was measured by MTT assay.The apoptosis and mitochondrial membrane potential in T-47D cells were analyzed by flow cytometry.Western blot and flow cytometry analysis were performed to evaluate the expression of DR5on T-47D cell surface and the activation of caspase-8and caspase-3.RESULTS:Imperatorin significantly enhanced the inhibition of cell viability induced by TRAIL of T-47D and MCF-7cells,and significantly increased the apoptosis of T-47D cells induced by TRAIL.Imperatorin treatment ob-viously induced upregulation of DR5expression and production of reactive oxygen species in the T-47D cells.In addition,imperatorin enhanced the TRAIL-induced damage of mitochondrial membrane potential and activation of caspase-8and caspase-3.CONCLUSION:Imperatorin enhances the anti-tumor effect of TRAIL on breast cancer via upregulating the expression of DR5.
作者
徐正阳
任瑞平
万鹏
袁祖国
XU Zhengyang;REN Ruiping;WAN Peng;YUAN Zuguo(Department of Radiotherapy and Chemotherapy, Ningbo Yinzhou People’s Hospital, Ningbo 315040 , China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2018年第1期81-86,共6页
Chinese Journal of Pathophysiology
基金
宁波市科学技术局市级科技计划项目(鄞科2017-59号)
