桔梗皂苷D诱导乳腺癌MDA-MB-231细胞凋亡  

Platycodin D induced apoptosis of breast cancer MDA-MB-231 cell

作　　者：孔亚[1] 王佳佳[1] 卢宗亮[1] 周蕊[1] 宋伟[1] 王贺[1] 许红霞[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所营养科,重庆400042

出　　处：《中国肿瘤生物治疗杂志》2016年第3期350-354,共5页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金资助项目(No.81171991)~~

摘　　要：目的:研究来自桔梗的天然单体化合物桔梗皂苷D(platycodin D,PD)对高转移性乳腺癌细胞MDA-MB-231凋亡的影响,初步探索其可能的作用机制。方法:以不同浓度(0、2.5、5、10μmol/L)PD处理乳腺癌MDA-MB-231细胞后,采用MTT法检测细胞增殖率并计算IC50值,流式细胞术检测细胞凋亡情况,Western blotting检测凋亡相关蛋白的表达水平。结果:PD呈剂量依赖性显著抑制MDA-MB-231细胞的增殖(P<0.01),作用72 h的IC50值为(7.30±2.67)μmol/L。与对照组相比,10μmol/L的PD可显著促进MDA-MB-231细胞的凋亡(P<0.05)。PD激活了caspase家族蛋白,上调有活性的cleaved caspase-3、cleaved caspase-8和cleaved caspase-9的表达,下调无活性的caspase-8和caspase-9的表达;PD同时减少Bcl-2的表达,增加Bax的表达,使Bcl-2/Bax的比值降低。研究还发现PD使突变型P53蛋白的表达减少、E2F1的表达增加。结论:PD抑制乳腺癌细胞增殖具有明显的抗肿瘤效应,而诱导凋亡的发生可能是其发挥抗肿瘤效应的机制之一。Objective： This study was designed to estimate the role of platycodin D（ PD）,a natural monomeric compound derived from platycodin grandiflorum,in apoptosis of highly metastatic breast cancer cell line MDA-MB-231 and to primarily explore the possible mechanisms. Methods： MDA-MB-231 cells were treated with different concentrations of PD（ 0,2. 5,5,10 μmol / L）,cell proliferation rate was detected by MTT and IC50 value was calculated; cell apoptosis was evaluated by Flow cytometry,and the expressions of apoptosis-related proteins were assessed by Western blotting. Results： PD significantly inhibited MDA-MB-231 cell proliferation（ P〈0. 01） in a dose-dependent manner with a IC50 value of（ 7. 30 ± 2. 67）μmol /L at 72 h. Compared with control group,10 μmol /L PD could significantly promote the apoptosis of MDA-MB-231cells（ P〈0. 05）. PD increased the caspase protein activity by up-regulating active cleaved caspase-3,-8 and-9 and downregulating inactive caspase-8 and-9. PD also decreased the expression level of Bcl-2 and increased Bax expression,resulting in the decrease of Bcl-2 / Bax ratio in MDA-MB-231 cells. The protein expression of mutant P53 was down-regulated after treated with PD; otherwise,the expression of E2F1 was up-regulated. Conclusion： PD had an obvious anticancer effect by inhibiting breast cancer cell proliferation,and inducing apoptosis might be a potential mechanism of anti-cancer effects.

关 键 词：桔梗皂苷D 乳腺癌 MDA-MB-231细胞 细胞凋亡 

分 类 号：R737.9[医药卫生—肿瘤] R730.5[医药卫生—临床医学]