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Abstract Title:

Psychological stress induces chemoresistance in breast cancer by upregulating mdr1.

Abstract Source:

Biochem Biophys Res Commun. 2005 Apr 15 ;329(3):888-97. PMID: 15752739

Abstract Author(s):

Fengxi Su, Nengyong Ouyang, Pengcheng Zhu, Nengtai Ouyang, Weijuan Jia, Chang Gong, Xuexia Ma, Huanbin Xu, Erwei Song

Article Affiliation:

Department of Breast Surgery, Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou 510120, PR China.

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.

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Sayer Ji
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