黄芩素对BCRP介导的人乳腺癌MCF-7/MX细胞多药耐药的逆转作用  

Effect of baicalein on reversal of multidrug resistance in MCF-7/MX cells in vitro and its mechanisms

作　　者：付乃洁 王畅 朱迪颖 刘临红 张慧丰 师锐赞 张明升 FU Nai-jie;WANG Chang;ZHU Di-ying;LIU Lin-hong;ZHANG hui-feng;SHI Rui-zan;ZHANG Ming-sheng(Dept of Pharmacology,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学基础医学院药理学教研室,山西太原030001

出　　处：《中国药理学通报》2018年第6期862-866,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81502641);山西医科大学校科技创新基金资助项目(No 01201308)

摘　　要：目的 探讨黄芩素对乳腺癌耐药蛋白(breast cancer resistance protein,BCRP)介导的人乳腺癌MCF-7/MX细胞多药耐药(multidrug resistance,MDR)的逆转作用及可能机制。方法 MTT法检测黄芩素对MCF-7/MX细胞的增殖抑制及耐药逆转作用;Western blot法检测黄芩素对MCF-7/MX细胞BCRP、p38 MAPK、p-p38 MAPK、核因子NF-κB p65蛋白表达的影响。结果 MCF-7/MX细胞对米托蒽醌、顺铂和氟尿嘧啶的耐药倍数分别为70.45、6.68、21.47。2.5、5μmol·L-1的黄芩素可增强MCF-7/MX细胞对上述化疗药的敏感性,下调BCRP表达,降低NF-κB p65蛋白表达和p38蛋白的磷酸化水平。结论 黄芩素可有效逆转BCRP介导的MCF-7/MX细胞的MDR,此作用可能与抑制p38 MAPK信号通路和NF-κB信号通路有关。Aim To investigate the effect of baicalein on the reversal of multidrug resistance（MDR） mediated by breast cancer resistance protein（BCRP） in human breast cancer MCF-7/MX cells,and explore the possible mechanisms. Methods MTT assay was performed to determine the cytotoxicity of baicalein and susceptibility of chemotherapeutic drugs. The protein expression levels of BCRP,p-p38 MAPK and NF-κB p65 were determined by Western blot. Results MCF-7/MX cells were not only resistant to MX but cross-resistant to 5-FU and DDP,and the resistance index was 70.45,6.68 and 21.47,respectively. 2.5,5μmol·L^（-1） of baicalein could increase the sensitivity to above chemotherapeutic agents and decrease the expression levels of BCRP, p-p38 MAPK and NF-κB p65 in MCF-7/MX cells. Conclusion Baicalein can effectively reverse MDR of MCF-7/MX by down-regulating BCRP expression through p38/MAPK and NF-κB pathways.

关 键 词：黄芩素 多药耐药 乳腺癌耐药蛋白 米托蒽醌 P-P38 NF-κB 

分 类 号：R284.1[医药卫生—中药学] R341[医药卫生—中医学]