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[Relationship between drug resistance and the expression of NF-kappaB induced in leukemic cells]

Xiao-hong Zhang1, Li-da Su, Qing-hua Lu

  • 1The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.

Zhejiang Da Xue Xue Bao. Yi Xue Ban = Journal of Zhejiang University. Medical Sciences
|October 12, 2004
PubMed
Abstract

Insights

Arsenic trioxide induces apoptosis in K562 cells by degrading IkappaB-alpha and activating NF-kappaB. However, K562/ADR cells show resistance to this apoptosis due to elevated NF-kappaB expression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Leukemic cells can develop drug resistance, impacting treatment efficacy.
  • Arsenic trioxide (As2O3) is a chemotherapeutic agent known to induce apoptosis.
  • The Nuclear Factor kappa B (NF-kappaB) pathway plays a crucial role in cell survival and drug resistance.

Purpose of the Study:

  • To investigate the relationship between drug resistance in leukemic cells and the expression of IkappaB-alpha and NF-kappaB.
  • To understand the mechanism of apoptosis induced by arsenic trioxide (As2O3) in K562 and K562/ADR cells.

Main Methods:

  • Induction of apoptosis in K562 and K562/ADR cells using varying concentrations of As2O3.
  • Western blot analysis to quantify NF-kappaB in the nucleus and IkappaB-alpha in the cytoplasm.
  • Flow cytometry to assess apoptosis and IkappaB-alpha protein degradation.

Main Results:

  • As2O3 treatment significantly reduced apoptosis in K562/ADR cells compared to K562 cells.
  • At 4 micromol/L As2O3, apoptosis increased to 50.56% in K562 cells but only to 8.00% in K562/ADR cells.
  • As2O3 induced IkappaB-alpha degradation and NF-kappaB activation in K562 cells, but not in K562/ADR cells.

Conclusions:

  • Arsenic trioxide effectively induces apoptosis in K562 cells through IkappaB-alpha degradation and NF-kappaB activation.
  • K562/ADR cells exhibit elevated NF-kappaB expression and resistance to As2O3-induced apoptosis.
  • The findings highlight the role of the NF-kappaB pathway in mediating As2O3 resistance in leukemic cells.

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