title: Synergistic cytotoxic effect of genistein and doxorubicin on drug-resistant human breast cancer MCF-7/Adr cells.
abstract: The molecular mechanisms underlying genistein-mediated reversal of chemoresistance remains unknown. In the present study, we investigated the molecular mechanisms by which genistein overcomes chemoresistance and its effect on doxorubicin-induced cytotoxicity. Consistent with previous reports, genistein combined with doxorubicin had a synergistic effect on MCF-7/Adr cells, and genistein reduced the chemoresistance of these cells. Genistein treatment increased the intracellular accumulation of doxorubicin but did not influence P-gp function. The combination of genistein and doxorubicin significantly induced cell cycle arrest and apoptosis. Genistein treatment strongly inhibited HER2/neu but not MDR-1 expression at both the mRNA and protein levels. Therefore, our results demonstrated that genistein combined with doxorubicin had a synergistic effect on MCF-7/Adr cells, and the mechanisms likely involve an increase in the intracellular accumulation of doxorubicin and suppression of HER2/neu expression.
authors.affiliation: Department of Endocrine and Vascular Surgery, Taihe Hospital, Hubei Medical College, Shiyan, Hubei 442000, P.R. China.
authors.forename: Jia-Peng
authors.initials: JP
authors.lastname: Xue
authors.affiliation: Department of Endocrine and Vascular Surgery, Taihe Hospital, Hubei Medical College, Shiyan, Hubei 442000, P.R. China.
authors.forename: Geng
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Endocrine and Vascular Surgery, Taihe Hospital, Hubei Medical College, Shiyan, Hubei 442000, P.R. China.
authors.forename: Zong-Bin
authors.initials: ZB
authors.lastname: Zhao
authors.affiliation: Department of Endocrine and Vascular Surgery, Taihe Hospital, Hubei Medical College, Shiyan, Hubei 442000, P.R. China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Endocrine and Vascular Surgery, Taihe Hospital, Hubei Medical College, Shiyan, Hubei 442000, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D004317:Doxorubicin; D019833:Genistein; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; C513055:ABCB1 protein, human; C508053:ERBB2 protein, human