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Article

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

  • Authors:
    • Feng Gao
    • Jia Liu
    • Wan Wei Dong
    • Wei Wang
    • Ying Wang
    • Dali Cai
    • Zhihong Zheng
    • Kailai Sun
  • View Affiliations / Copyright

    Affiliations: Department of Genetics, China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China, Laboratory Animal Center, China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China, The First Hospital of China Medical University, Heping, Shenyang, Liaoning 110001, P.R. China
  • Pages: 926-932
    |
    Published online on: December 16, 2013
       https://doi.org/10.3892/or.2013.2930
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Gao F, Liu J, Dong WW, Wang W, Wang Y, Cai D, Zheng Z and Sun K: Investigation of the mechanism involved in the As2O3-regulated decrease in MDR1 expression in leukemia cells. Oncol Rep 31: 926-932, 2014.
APA
Gao, F., Liu, J., Dong, W.W., Wang, W., Wang, Y., Cai, D. ... Sun, K. (2014). Investigation of the mechanism involved in the As2O3-regulated decrease in MDR1 expression in leukemia cells. Oncology Reports, 31, 926-932. https://doi.org/10.3892/or.2013.2930
MLA
Gao, F., Liu, J., Dong, W. W., Wang, W., Wang, Y., Cai, D., Zheng, Z., Sun, K."Investigation of the mechanism involved in the As2O3-regulated decrease in MDR1 expression in leukemia cells". Oncology Reports 31.2 (2014): 926-932.
Chicago
Gao, F., Liu, J., Dong, W. W., Wang, W., Wang, Y., Cai, D., Zheng, Z., Sun, K."Investigation of the mechanism involved in the As2O3-regulated decrease in MDR1 expression in leukemia cells". Oncology Reports 31, no. 2 (2014): 926-932. https://doi.org/10.3892/or.2013.2930
Copy and paste a formatted citation
x
Spandidos Publications style
Gao F, Liu J, Dong WW, Wang W, Wang Y, Cai D, Zheng Z and Sun K: Investigation of the mechanism involved in the As2O3-regulated decrease in MDR1 expression in leukemia cells. Oncol Rep 31: 926-932, 2014.
APA
Gao, F., Liu, J., Dong, W.W., Wang, W., Wang, Y., Cai, D. ... Sun, K. (2014). Investigation of the mechanism involved in the As2O3-regulated decrease in MDR1 expression in leukemia cells. Oncology Reports, 31, 926-932. https://doi.org/10.3892/or.2013.2930
MLA
Gao, F., Liu, J., Dong, W. W., Wang, W., Wang, Y., Cai, D., Zheng, Z., Sun, K."Investigation of the mechanism involved in the As2O3-regulated decrease in MDR1 expression in leukemia cells". Oncology Reports 31.2 (2014): 926-932.
Chicago
Gao, F., Liu, J., Dong, W. W., Wang, W., Wang, Y., Cai, D., Zheng, Z., Sun, K."Investigation of the mechanism involved in the As2O3-regulated decrease in MDR1 expression in leukemia cells". Oncology Reports 31, no. 2 (2014): 926-932. https://doi.org/10.3892/or.2013.2930
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