Up-regulation of P-glycoprotein confers acquired resistance to 6-mercaptopurine in human chronic myeloid leukemia cells

  • Authors:
    • Xing-Xiang Peng
    • Zhi Shi
    • Amit K. Tiwari
    • Vijaya L. Damaraju
    • Liwu Fu
    • Carol E. Cass
    • Charles E. Ashby
    • Gary D. Kruh
    • Zhe-Sheng Chen
  • View Affiliations

  • Published online on: March 21, 2011     https://doi.org/10.3892/ol.2011.288
  • Pages: 549-556
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Abstract

To investigate the mechanisms of cellular resistance to 6-mercaptopurine (6-MP) in chronic myeloid leukemia (CML), a 6-MP resistant cell line (K562-MP5) was established by stepwise selection of the CML cell line (K562). The results of the drug sensitivity analysis of the K562-MP5 cell line revealed the cells to be 339-fold more resistant to 6-MP compared with the parental K562 cells. K562-MP5 cells exhibited decreased accumulation and increased efflux of [14C]6-MP and its metabolites. In addition, K562-MP5 cells showed increased [3H]MTX transport. K562-MP5 cells over‑expressed P-glycoprotein (P-gp) and up-regulated MDR1 mRNA levels. Taken together, these results suggest that the up-regulation of P-gp, which contributes to the decreased accumulation by increasing the efflux of 6-MP and its metabolites, underlies the mechanism of 6-MP resistance in K562 cells.
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May-June 2011
Volume 2 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Peng X, Shi Z, Tiwari AK, Damaraju VL, Fu L, Cass CE, Ashby CE, Kruh GD and Chen Z: Up-regulation of P-glycoprotein confers acquired resistance to 6-mercaptopurine in human chronic myeloid leukemia cells. Oncol Lett 2: 549-556, 2011
APA
Peng, X., Shi, Z., Tiwari, A.K., Damaraju, V.L., Fu, L., Cass, C.E. ... Chen, Z. (2011). Up-regulation of P-glycoprotein confers acquired resistance to 6-mercaptopurine in human chronic myeloid leukemia cells. Oncology Letters, 2, 549-556. https://doi.org/10.3892/ol.2011.288
MLA
Peng, X., Shi, Z., Tiwari, A. K., Damaraju, V. L., Fu, L., Cass, C. E., Ashby, C. E., Kruh, G. D., Chen, Z."Up-regulation of P-glycoprotein confers acquired resistance to 6-mercaptopurine in human chronic myeloid leukemia cells". Oncology Letters 2.3 (2011): 549-556.
Chicago
Peng, X., Shi, Z., Tiwari, A. K., Damaraju, V. L., Fu, L., Cass, C. E., Ashby, C. E., Kruh, G. D., Chen, Z."Up-regulation of P-glycoprotein confers acquired resistance to 6-mercaptopurine in human chronic myeloid leukemia cells". Oncology Letters 2, no. 3 (2011): 549-556. https://doi.org/10.3892/ol.2011.288