title: Dioscin strengthens the efficiency of adriamycin in MCF-7 and MCF-7/ADR cells through autophagy induction: More than just down-regulation of MDR1.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.|Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.|Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Huo
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.|Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.|Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.|Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.|Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.|Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.|Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China.|Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D016328:NF-kappa B; C019357:dioscin; D004317:Doxorubicin; D004144:Diosgenin