丹参酮Ⅱ_(A)对阿霉素耐药人乳腺癌细胞的多药耐药逆转作用及机制研究  

Reversal effect and mechanism of tanshinone Ⅱ_(A) on multidrug resistance of doxorubicin-resistant human breast cancer cells

作　　者：宁玉明 潘一帆 李范珠[2] NING Yu-ming;PAN Yi-fan;LI Fan-zhu(Hangzhou Fuyang Women and Children Hospital,Hangzhou 311400,China;College of Pharmaceutical Science,Zhejiang Chinese Medical University,Hangzhou 311400,China)

机构地区：[1]杭州市富阳区妇幼保健院,浙江杭州311400 [2]浙江中医药大学药学院,浙江杭州311400

出　　处：《中草药》2021年第22期6890-6896,共7页Chinese Traditional and Herbal Drugs

基　　金：杭州市科技计划项目(20171226Y187)。

摘　　要：目的研究丹参酮Ⅱ_(A)对阿霉素耐药人乳腺癌细胞MCF-7/ADR的多药耐药逆转作用及相关机制。方法分别用丹参酮Ⅱ_(A)、阿霉素、阿霉素联合丹参酮Ⅱ_(A)处理人乳腺癌MCF-7细胞和MCF-7/ADR细胞,采用MTT法检测细胞增殖率;流式细胞术检测丹参酮Ⅱ_(A)干预后MCF-7/ADR细胞内阿霉素蓄积量的变化;检测丹参酮Ⅱ_(A)干预后MCF-7/ADR细胞三磷酸腺苷(adenosine triphosphate,ATP)消耗量的变化;采用qRT-PCR、Western blotting法检测丹参酮Ⅱ_(A)干预后MCF-7/ADR细胞ATP结合转运蛋白B1(ATP-binding cassettetransporter B1,ABCB1)、ABCG2和ABCC1基因和蛋白表达的变化。结果丹参酮Ⅱ_(A)显著抑制MCF-7及MCF-7/ADR细胞增殖(P<0.05),呈剂量相关性;丹参酮Ⅱ_(A)能够逆转MCF-7/ADR细胞的多药耐药性(P<0.05),增加MCF-7/ADR细胞内阿霉素的蓄积(P<0.05),减少MCF-7/ADR细胞的ATP消耗(P<0.05),显著下调ABCC1和ABCG2基因和蛋白表达(P<0.05)。结论丹参酮Ⅱ_(A)能够通过调控ABCG2、ABCC1介导的转运,逆转MCF-7/ADR细胞的多药耐药性。ObjectiveTo study the reversal effect of tanshinone Ⅱ_(A)on multidrug resistance of doxorubicin-resistant human breast cancer cells MCF-7/ADR and related mechanisms.Methods Human breast cancer MCF-7 cells and MCF-7/ADR cells were respectively treated with tanshinone Ⅱ_(A),doxorubicin,doxorubicin+tanshinone Ⅱ_(A),cell proliferation rate was detected by MTT method;Doxorubicin accumulation inMCF-7/ADR cellsafter tanshinone Ⅱ_(A)intervention was detected by flow cytometry;Change of adenosine triphosphate(ATP)consumption in MCF-7/ADR cells after tanshinone Ⅱ_(A)interventionwas detected;qRT-PCR and Western blotting were used to detect ATP-binding cassettetransporter B1(ABCB1),ABCG2and ABCC1genes and protein expressionsin MCF-7/ADR cells after tanshinone Ⅱ_(A)intervention.Results Tanshinone Ⅱ_(A)significantly inhibited the cell proliferation of MCF-7 and MCF-7/ADRcells(P<0.05),with dose-dependent;Tanshinone Ⅱ_(A)reversedthe multidrug resistance of MCF-7/ADR cells(P<0.05),increasedthe accumulation of doxorubicin in MCF-7/ADR cells(P<0.05),reducedthe ATP consumption of MCF-7/ADR cells(P<0.05),down-regulatedthe expressionsof ABCC1and ABCG2genes and proteins(P<0.05).Conclusion Tanshinone Ⅱ_(A)can reverse the multidrug resistance of MCF-7/ADR cells by regulating the transport mediated by ABCG2 and ABCC1.

关 键 词：丹参酮Ⅱ_(A) 阿霉素 乳腺癌 多药耐药 ABC转运蛋白 

分 类 号：R285.5[医药卫生—中药学]