title: Psychological stress induces chemoresistance in breast cancer by upregulating mdr1.
abstract: Psychological distress reduces the efficacy of chemotherapy in breast cancer patients. The mechanism may be related to the altered neuronal or hormonal secretions during stress. Here, we reported that adrenaline, a hormone mediating the biological activities of stress, upregulates mdr1 gene expression in MCF-7 breast cancer cells via alpha(2)-adrenergic receptors in a dose-dependent manner. Mdr1 upregulation can be specifically inhibited by pretreatment with mdr1-siRNA. Consequently, adrenergic stimulation enhances the pump function of P-glycoprotein and confers resistance of MCF-7 cells to paclitaxel. In vivo, restraint stress increases mdr1 gene expression in the MCF-7 cancers that are inoculated subcutaneously into the SCID mice and provokes resistance to doxorubicin in the implanted tumors. The effect can be blocked by injection of yohimbine, an alpha(2)-adrenergic inhibitor, but not by metyrapone, a corticosterone synthesis blocker. Therefore, we conclude that breast cancers may develop resistance against chemotherapeutic drugs under psychological distress by over-expressing mdr1 via adrenergic stimulation.
authors.affiliation: Department of Breast Surgery, Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou 510120, PR China.
authors.forename: Fengxi
authors.initials: F
authors.lastname: Su
authors.forename: Nengyong
authors.initials: N
authors.lastname: Ouyang
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Zhu
authors.forename: Nengtai
authors.initials: N
authors.lastname: Ouyang
authors.forename: Weijuan
authors.initials: W
authors.lastname: Jia
authors.forename: Chang
authors.initials: C
authors.lastname: Gong
authors.forename: Xuexia
authors.initials: X
authors.lastname: Ma
authors.forename: Huanbin
authors.initials: H
authors.lastname: Xu
authors.forename: Erwei
authors.initials: E
authors.lastname: Song
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D017239:Paclitaxel; D004837:Epinephrine