丹参酮ⅡA对乳腺癌细胞阿霉素化疗敏感度的影响及相关机制  

Tanshinone ⅡA Enhances Chemosensitivity of Breast Cancer Cells to Doxorubicin and Related Mechanism

作　　者：袁源[1] 赵千 胡占升 YUAN Yuan;ZHAO Qian;HU Zhansheng(Department of Pharmacy,The Central Hospital of Jinzhou,Jinzhou 121000,China;Department of Clinical Laboratory,The Third Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,China;Department of Intensive Care Unit,The First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000,China)

机构地区：[1]锦州市中心医院药学部,锦州121000 [2]锦州医科大学附属第三医院检验科,锦州121000 [3]锦州医科大学附属第一医院重症医学科,锦州121000

出　　处：《肿瘤防治研究》2019年第7期594-599,共6页Cancer Research on Prevention and Treatment

摘　　要：目的探讨丹参酮ⅡA对人乳腺癌MCF-7及MDA-MB-231细胞阿霉素化疗敏感度的影响及相关机制。方法用不同浓度的丹参酮ⅡA处理人乳腺癌MCF-7及MDA-MB-231细胞,MTS法检测丹参酮ⅡA对MCF-7及MDA-MB-231细胞增殖的影响,并筛选无毒计量的丹参酮ⅡA用于实验。用无毒剂量的丹参酮ⅡA干预不同浓度阿霉素处理的MCF-7及MDA-MB-231细胞,MTS法检测干预前后细胞增殖的变化;流式细胞法检测干预前后细胞凋亡和乳腺癌干细胞表面标志物CD44+/CD24-/low表达的变化以及细胞内阿霉素积累的变化;Western blot检测干预前后P-gp、BCRP、MRP1蛋白的表达变化。结果丹参酮ⅡA剂量依赖性抑制MCF-7及MDA-MB-231细胞的增殖;与单用阿霉素相比较,阿霉素与无毒剂量的丹参酮ⅡA联合应用后MCF-7及MDA-MB-231细胞的增殖减慢;无毒剂量的丹参酮ⅡA明显增强了阿霉素诱导乳腺癌细胞凋亡(均P<0.05)及杀死乳腺癌干细胞(P=0.048)的能力、明显增加了阿霉素在乳腺癌细胞内的积累(均P<0.05)、下调了阿霉素处理的乳腺癌细胞外排型ABC转运蛋白P-gp、BCRP及MRP1的表达(均P<0.05)。结论丹参酮ⅡA能够增强阿霉素乳腺癌化疗的敏感度,其机制可能与下调P-gp、BCRP及MRP1的表达有关。Objective To investigate the effects and mechanisms of tanshinone ⅡA on the chemosensitivity of human breast cancer MCF-7 and MDA-MB-231 cells to doxorubicin. Methods Human breast cancer MCF-7 and MDA-MB-231 cells were treated with different concentrations of tanshinone ⅡA. The effect of tanshinone ⅡA on the proliferation of MCF-7 and MDA-MB-231 cells were assessed by MTS assay, and nontoxic dose of tanshinone ⅡA was screened. MCF-7 and MDA-MB-231 cells were exposed to different concentrations of doxorubicin with or without nontoxic dose of tanshinone ⅡA intervention. Cell proliferation was measured by MTS assay;cell apoptotic rate, the expression of CD44+/CD24-/low as a surface marker of breast cancer stem cells and intracellular doxorubicin accumulation were analyzed by flow cytometry;the expressions of P-gp, BCRP and MRP1 were detected by Western blot. Results Tanshinone ⅡA inhibited the proliferation of MCF-7 and MDA-MB-231 cells in a dose-dependent manner;compared with doxorubicin alone, MCF-7 and MDA-MB-231 cells treated with doxorubicin combined with nontoxic dose of tanshinone ⅡA exhibited a slower growth rate;nontoxic doses of tanshinone ⅡA significantly enhanced the abilities of doxorubicin to induce the apoptosis of breast cancer cells (all P<0.05) and kill breast cancer stem cells (P=0.048), promoted the accumulations of doxorubicin in breast cancer cells (all P<0.05) and down-regulated the expressions of P-gp, BCRP and MRP1 in doxorubicin-treated breast cancer cells (all P<0.05). Conclusion Tanshinone ⅡA could enhance the chemosensitivity of breast cancer cells to doxorubicin, and the mechanism may be related to the down-regulation of P-gp, BCRP and MRP1 expression.

关 键 词：丹参酮ⅡA 阿霉素 乳腺癌干细胞 外排型ABC转运蛋白 

分 类 号：R737.9[医药卫生—肿瘤]