title: Tetramethylpyrazine reverses multidrug resistance in breast cancer cells through regulating the expression and function of P-glycoprotein.
abstract: Tumor multidrug resistance (MDR) has become the major obstacle to cancer chemotherapy. Recent studies suggest that tetramethylpyrazine (TMP) could reverse tumor MDR although the mechanism by which TMP overcomes tumor MDR remains elusive. Therefore, in this study, we examined the effects of TMP on MDR in drug-resistant breast cancer cells and investigated the underlying mechanisms. MCF-7 cells and the derived P-glycoprotein (Pgp) overexpressing MCF-7/dox cells were treated with TMP, and their growth was examined by MTT assay. Doxorubicin accumulation in the cells was evaluated by flow cytometry, and the expression of Pgp was detected by Western blot and RT-PCR analysis. The results showed that TMP increased the intracellular concentration of doxorubicin and inhibited Pgp-mediated efflux of doxorubicin in a dose-dependent manner. Moreover, TMP inhibited the ATPase activity of P-gp and suppressed the expression of Pgp in MCF-7/dox cells. Taken together, these data suggest that TMP has potential application in the treatment of chemotherapy-resistant breast cancer.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Liaoning Medical University, 121001 Jinzhou, Liaoning, China. zhangyinxu@163.com
authors.forename: Yinxu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Liu
authors.forename: Teng
authors.initials: T
authors.lastname: Zuo
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Jun Hua
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D011719:Pyrazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000903:Antibiotics, Antineoplastic; D011719:Pyrazines; D012333:RNA, Messenger; D014665:Vasodilator Agents; D004317:Doxorubicin; D000251:Adenosine Triphosphatases; C017953:tetramethylpyrazine