[Effect of regulation of Y-box protein 1 by RNA interference on the doxorubicin induced mdr1 gene expression in K562

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Hui-Ling Shen1, Wen-Lin Xu, Qiao-Yun Chen

  • 1Department of Central Laboratory, the Affiliated People's Hospital of Jiangsu University, Zhenjiang 212002, China.

Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi
|July 26, 2011
PubMed
Abstract

Insights

Doxorubicin (DOX) induces multidrug resistance 1 (mdr1) gene expression in K562 cells. This is mediated by the Y-box binding protein 1 (YB-1), which translocates to the nucleus and activates mdr1 transcription.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Multidrug resistance (MDR) is a major challenge in cancer chemotherapy.
  • The mdr1 gene encodes P-glycoprotein (P-gp), a key efflux pump in MDR.
  • YB-1 is a transcription factor implicated in cellular stress responses and gene regulation.

Purpose of the Study:

  • To elucidate the role of YB-1 in doxorubicin-induced mdr1 gene expression in K562 cells.

Main Methods:

  • K562 cells were treated with doxorubicin (DOX).
  • Gene and protein expression (mdr1, YB-1, P-gp) were analyzed using RT-PCR, flow cytometry, and Western blotting.
  • YB-1 expression was inhibited using RNA interference (RNAi).

Main Results:

  • DOX treatment increased mdr1 and P-gp expression in K562 cells.
  • DOX also upregulated YB-1 expression and promoted its nuclear translocation.
  • Silencing YB-1 significantly reduced mdr1 and P-gp expression in DOX-treated cells.

Conclusions:

  • Doxorubicin induces mdr1 gene expression in K562 cells.
  • Activated YB-1 appears to be a key mediator in the transcriptional regulation of mdr1 by doxorubicin.

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