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Sorcin, an important gene associated with multidrug-resistance in human leukemia cells

Yuan Zhou1, Yuanfu Xu, Yaohong Tan

  • 1Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.

Leukemia Research
|October 11, 2005
PubMed

Insights

Sorcin, a calcium-binding protein, drives multi-drug resistance (MDR) in leukemia cells. Inhibiting sorcin can reverse this resistance, offering potential therapeutic strategies for leukemia treatment.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Sorcin (soluble resistance-related calcium-binding protein) is a 22kD calcium-binding protein found in multi-drug resistant (MDR) cell lines.
  • Sorcin expression is significantly upregulated in doxorubicin-induced MDR leukemia cells (K562/A02) compared to parent cells.
  • In leukemia patients, sorcin expression correlates with the mdr1 gene and inversely with chemotherapy response and prognosis.

Purpose of the Study:

  • To investigate the specific contribution of sorcin to the drug-resistant phenotype in K562 leukemia cells.
  • To determine if manipulating sorcin levels affects resistance to various chemotherapeutic agents.

Main Methods:

  • Overexpression of sorcin protein in K562 cells via gene transfection.
  • Inhibition of sorcin expression using sorcin-targeting small interfering RNA (siRNA) in MDR K562/A02 and sorcin-transfected K562 cells.

Main Results:

  • Sorcin overexpression in K562 cells conferred increased drug resistance (4.1- to 22.5-fold) to doxorubicin, etoposide, homoharringtonine, and vincristine.
  • Inhibition of sorcin expression using siRNA partially reversed drug resistance in both MDR K562/A02 and sorcin-transfected K562 cells.

Conclusions:

  • Sorcin plays a significant role in the development of multi-drug resistance in leukemia cells.
  • Targeting sorcin expression may be a viable strategy to overcome chemotherapy resistance in leukemia.

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