Psychological stress induces chemoresistance in breast cancer by upregulating mdr1

Biochem Biophys Res Commun. 2005 Apr 15;329(3):888-97. doi: 10.1016/j.bbrc.2005.02.056.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Epinephrine / pharmacology
  • Female
  • Humans
  • Mice
  • Mice, SCID
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacokinetics*
  • Stress, Psychological / complications*
  • Stress, Psychological / metabolism*
  • Treatment Outcome
  • Up-Regulation / drug effects


  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Paclitaxel
  • Epinephrine