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Article

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 / Copyright

    Affiliations: Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Queens, NY 11439, USA, Department of Oncology, Cross Cancer Institute and University of Alberta, Edmonton, AB, Canada, State Key Laboratory for Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, P.R. China, UIC Cancer Center, University of Illinois at Chicago College of Medicine, Chicago, IL 60612, USA, Department of Psychiatry and Pharmacology, School of Medicine, New York University, New York, NY 10016, USA
  • Pages: 549-556
    |
    Published online on: March 21, 2011
       https://doi.org/10.3892/ol.2011.288
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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