[关键词]
[摘要]
目的 研究丹参酮IIA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IIA、阿霉素、阿霉素联合丹参酮IIA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IIA干预后MCF-7/ADR细胞内阿霉素蓄积量的变化;检测丹参酮IIA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IIA干预后MCF-7/ADR细胞ATP结合转运蛋白B1(ATP-binding cassette transporter B1,ABCB1)、ABCG2和ABCC1基因和蛋白表达的变化。结果 丹参酮IIA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IIA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IIA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。
[Key word]
[Abstract]
Objective To study the reversal effect of tanshinone IIA 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 IIA, doxorubicin, doxorubicin + tanshinone IIA, cell proliferation rate was detected by MTT method; Doxorubicin accumulation in MCF-7/ADR cells after tanshinone IIA intervention was detected by flow cytometry; Change of adenosine triphosphate (ATP) consumption in MCF-7/ADR cells after tanshinone IIA intervention was detected; qRT-PCR and Western blotting were used to detect ATP-binding cassette transporter B1 (ABCB1), ABCG2 and ABCC1 genes and protein expressions in MCF-7/ADR cells after tanshinone IIA intervention. Results Tanshinone IIA significantly inhibited the cell proliferation of MCF-7 and MCF-7/ADR cells (P<0.05), with dose-dependent; Tanshinone IIA reversed the multidrug resistance of MCF-7/ADR cells (P<0.05), increased the accumulation of doxorubicin in MCF-7/ADR cells (P<0.05), reduced the ATP consumption of MCF-7/ADR cells (P<0.05), down-regulated the expressions of ABCC1 and ABCG2 genes and proteins (P<0.05). Conclusion Tanshinone IIA can reverse the multidrug resistance of MCF-7/ADR cells by regulating the transport mediated by ABCG2 and ABCC1.
[中图分类号]
R285.5
[基金项目]
杭州市科技计划项目(20171226Y187)