Dioscin strengthens the efficiency of adriamycin in MCF-7 and MCF-7/ADR cells through autophagy induction: More than just down-regulation of MDR1.
Dioscin strengthens the efficiency of adriamycin in MCF-7 and MCF-7/ADR cells through autophagy induction: More than just down-regulation of MDR1.
复制标题
薯蓣皂苷通过诱导自噬增强阿霉素在 MCF-7 和 MCF-7/ADR 细胞中的效率：不仅仅是下调 MDR1
DOI：
10.1038/srep28403
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发表时间：
2016-06-22
影响因子：
4.6
通讯作者：
Liu K
中科院分区：
文献类型：
--
作者：
Wang C;Huo X;Wang L;Meng Q;Liu Z;Liu Q;Sun H;Sun P;Peng J;Liu K
本研究旨在观察薯蓣皂苷对阿霉素（ADR）敏感（MCF-7）和耐药（MCF-7/ADR）人乳腺癌细胞ADR活性的影响，并探讨其分子机制。薯蓣皂苷可增强ADR对MCF-7和MCF-7/ADR细胞的增殖抑制作用。薯蓣皂苷可显著抑制MCF-7/ADR细胞MDR 1 mRNA和蛋白表达，抑制MDR 1启动子和核因子κ B（NF-κB）活性。此外，薯蓣皂苷还可抑制抑制剂κB-α（IκB-α）的降解。薯蓣皂苷可诱导MCF-7和MCF-7/ADR细胞胞浆内空泡形成，并诱导LC 3-II蛋白表达。自噬抑制剂3-MA可阻断薯蓣皂苷对ADR细胞毒作用的影响。薯蓣皂苷抑制PI 3 K和Akt的磷酸化，导致LC 3-II表达上调。结论：薯蓣皂苷通过抑制NF-κB信号通路，下调MDR 1表达，增加MCF-7/ADR细胞对阿霉素的化疗敏感性。薯蓣皂苷通过抑制MCF-7和MCF-7/ADR细胞中PI 3 K/AKT通路诱导自噬，减轻ADR的细胞毒性。这些发现为进一步研究薯蓣皂苷作为化疗辅助剂的临床应用提供了证据。
The purpose of present study was to investigate the effect of dioscin on activity of adriamycin (ADR) in ADR-sensitive (MCF-7) and ADR-resistant (MCF-7/ADR) human breast cancer cells and to clarify the molecular mechanisms involved. Antiproliferation effect of ADR was enhanced by dioscin in MCF-7 and MCF-7/ADR cells. Dioscin significantly inhibited MDR1 mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activity in MCF-7/ADR cells. Additionally, inhibitor κB-α (IκB-α) degradation was inhibited by dioscin. Moreover, dioscin induced the formation of vacuoles in the cytoplasm and protein level of LC3-II in MCF-7 and MCF-7/ADR cells. Autophagy inhibitor 3-MA abolished the effect of dioscin on ADR cytotoxicity. Dioscin inhibited phosphorylation of PI3K and Akt, resulting in upregulation of LC3-II expression. In conclusion, dioscin increased ADR chemosensitivity by down-regulating MDR1 expression through NF-κB signaling inhibition in MCF-7/ADR cells. Autophagy was induced by dioscin to ameliorate the cytotoxicity of ADR via inhibition of the PI3K/AKT pathways in MCF-7 and MCF-7/ADR cells. These findings provide evidence in support of further investigation into the clinical application of dioscin as a chemotherapy adjuvant.