Investigation of the mechanism involved in the As2O3-regulated decrease in MDR1 expression in leukemia cells

Oncology Reports
Feng GaoKailai Sun

Abstract

Arsenic trioxide (As2O3) inhibits the expression of P-glycoprotein (P-gp) in leukemia cells; however, the mechanism behind this inhibition is unclear. The present study aimed to explore the effect of As2O3 on the expression and regulation of P-gp in leukemia cells, and elucidate the mechanism of the reversal of drug resistance. In the present study, electrophoretic mobility shift assay results indicated that p65 binds to the NF-κB binding site of MDR1, specifically in K562/D cells. Expression of p65 and phosphorylated IκB was reduced, while the expression of IκB was increased in K562/D cells treated with As2O3. The activity of luciferase increased up to 9-fold with 40 ng/ml TNF-α, and it was suppressed by ~25% following treatment with 1 µM As2O3. These findings suggest that As2O3 reverses the P-gp-induced drug resistance of leukemia cells through the NF-κB pathway. As2O3 may inhibit the activity of phosphorylase to inhibit IκB phosphorylation, thereby inhibiting NF-κB activity and MDR1 gene expression, leading to reversal of drug resistance.

References

Oct 1, 1987·Human Genetics·D F CallenI B Roninson
Oct 4, 1995·Biochemical and Biophysical Research Communications·K I Hirsch-ErnstG F Kahl
May 15, 1997·European Journal of Biochemistry·O FardelA Guillouzo
Feb 25, 2000·Therapeutic Drug Monitoring·Y Tanigawara
Apr 29, 2000·Nature·K M RyanK H Vousden
Oct 12, 2002·Carcinogenesis·Jason A Bush, Gang Li
Apr 25, 2003·Cancer Control : Journal of the Moffitt Cancer Center·Hilary Thomas, Helen M Coley
Aug 18, 2004·Biochemical Pharmacology·Vincent Quivy, Carine Van Lint
Mar 27, 2007·Annals of the New York Academy of Sciences·Julie Mathieu, Françoise Besançon
Sep 19, 2009·Trends in Pharmacological Sciences·Matthew D HallMichael M Gottesman

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