Butorphanol, a synthetic opioid, sensitizes ABCB1-mediated multidrug resistance via inhibition of the efflux function of ABCB1 in leukemia cells

  • Authors:
    • Jing Wen
    • Tao Zhang
    • Zhi-Ming Shan
    • Min-Yue Qi
    • Huan-Huan Xiu
    • Lei Liu
    • Shi-Zhe Wu
    • Zhen Jia
    • Kang-Qing Xu
  • View Affiliations

  • Published online on: June 11, 2015     https://doi.org/10.3892/or.2015.4052
  • Pages: 755-762
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Abstract

Multidrug resistance (MDR) remains a formidable challenge in the use of chemotherapy and represents a powerful obstacle to the treatment of leukemia. ATP-binding cassette subfamily B member 1 (ABCB1) is a recognized factor which causes MDR and is closely related to poor outcome and relapse in leukemia. Ongoing research concerning the strategy for inhibiting the abnormally high activity of the ABCB1 transporter is critically needed. In the present study, we sought to elucidate the interaction between ABCB1 transporter and butorphanol. Our results showed that butorphanol significantly antagonized ABCB1-mediated drug efflux and increased the intracellular drug concentration by inhibiting the transport activity of ABCB1 in leukemia cells. Mechanistic investigations demonstrated that butorphanol did not alter the protein expression or localization of ABCB1 in HL60/VCR and K562/ADR cells. Furthermore, homology modeling indicated that butorphanol could fit into the large drug-binding cavity of ABCB1 and form a binding conformation. In conclusion, butorphanol reversed the ABCB1-mediated MDR in leukemia cells by directly suppressing the efflux activity of ABCB1.
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August-2015
Volume 34 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wen J, Zhang T, Shan Z, Qi M, Xiu H, Liu L, Wu S, Jia Z and Xu K: Butorphanol, a synthetic opioid, sensitizes ABCB1-mediated multidrug resistance via inhibition of the efflux function of ABCB1 in leukemia cells. Oncol Rep 34: 755-762, 2015
APA
Wen, J., Zhang, T., Shan, Z., Qi, M., Xiu, H., Liu, L. ... Xu, K. (2015). Butorphanol, a synthetic opioid, sensitizes ABCB1-mediated multidrug resistance via inhibition of the efflux function of ABCB1 in leukemia cells. Oncology Reports, 34, 755-762. https://doi.org/10.3892/or.2015.4052
MLA
Wen, J., Zhang, T., Shan, Z., Qi, M., Xiu, H., Liu, L., Wu, S., Jia, Z., Xu, K."Butorphanol, a synthetic opioid, sensitizes ABCB1-mediated multidrug resistance via inhibition of the efflux function of ABCB1 in leukemia cells". Oncology Reports 34.2 (2015): 755-762.
Chicago
Wen, J., Zhang, T., Shan, Z., Qi, M., Xiu, H., Liu, L., Wu, S., Jia, Z., Xu, K."Butorphanol, a synthetic opioid, sensitizes ABCB1-mediated multidrug resistance via inhibition of the efflux function of ABCB1 in leukemia cells". Oncology Reports 34, no. 2 (2015): 755-762. https://doi.org/10.3892/or.2015.4052