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Article

Ponatinib enhances anticancer drug sensitivity in MRP7-overexpressing cells

  • Authors:
    • Yue-Li Sun
    • Priyank Kumar
    • Kamlesh Sodani
    • Atish Patel
    • Yihang Pan
    • Maria R. Baer
    • Zhe-Sheng Chen
    • Wen-Qi Jiang
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, P.R. China, Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professionals, St. John's University, Queens, New York, NY 11439, USA, Cytogenetics Laboratory, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA, University of Maryland Greenebaum Cancer Center and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA, Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
  • Pages: 1605-1612
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    Published online on: January 28, 2014
       https://doi.org/10.3892/or.2014.3002
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Abstract

The presence of acquired multidrug resistance (MDR) is one of the primary impediments to the success of chemotherapy. MDR is often a result of overexpression of ATP-binding cassette (ABC) transporters, which are involved in the extrusion of therapeutic drugs. Recently, it was shown that several ABC transporters could be modulated by specific tyrosine-kinase inhibitors (TKIs). Ponatinib, a multi-targeted TKI, inhibits the activity of BCR-ABL with very high potency and broad specificity, including the T315I mutation which confers resistance to other TKIs. It was reported that ponatinib was capable of reversing breast cancer resistance protein (BCRP)- and P-glycoprotein (P-gp)-mediated MDR. In the present study, we report for the first time that ponatinib also potentiates the cytotoxicity of widely used therapeutic substrates of MRP7, such as paclitaxel, docetaxel, vincristine and vinblastine. Ponatinib significantly enhances the accumulation of [3H]-paclitaxel in cells expressing MRP7. Furthermore, accumulation of [3H]-paclitaxel was achieved by inhibition of MRP7-mediated transport. Ponatinb limited drug export via MRP7 by multiple mechanisms. In addition to inhibition of pump function, ponatinib also downregulated MRP7 protein expression in a time- and concentration-dependent manner. Thus, ponatinib may represent a potential reversal agent for the treatment of MDR and may be useful for combination therapy in MDR cancer patients in clinical practice.
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Copy and paste a formatted citation
Spandidos Publications style
Sun Y, Kumar P, Sodani K, Patel A, Pan Y, Baer MR, Chen Z and Jiang W: Ponatinib enhances anticancer drug sensitivity in MRP7-overexpressing cells. Oncol Rep 31: 1605-1612, 2014.
APA
Sun, Y., Kumar, P., Sodani, K., Patel, A., Pan, Y., Baer, M.R. ... Jiang, W. (2014). Ponatinib enhances anticancer drug sensitivity in MRP7-overexpressing cells. Oncology Reports, 31, 1605-1612. https://doi.org/10.3892/or.2014.3002
MLA
Sun, Y., Kumar, P., Sodani, K., Patel, A., Pan, Y., Baer, M. R., Chen, Z., Jiang, W."Ponatinib enhances anticancer drug sensitivity in MRP7-overexpressing cells". Oncology Reports 31.4 (2014): 1605-1612.
Chicago
Sun, Y., Kumar, P., Sodani, K., Patel, A., Pan, Y., Baer, M. R., Chen, Z., Jiang, W."Ponatinib enhances anticancer drug sensitivity in MRP7-overexpressing cells". Oncology Reports 31, no. 4 (2014): 1605-1612. https://doi.org/10.3892/or.2014.3002
Copy and paste a formatted citation
x
Spandidos Publications style
Sun Y, Kumar P, Sodani K, Patel A, Pan Y, Baer MR, Chen Z and Jiang W: Ponatinib enhances anticancer drug sensitivity in MRP7-overexpressing cells. Oncol Rep 31: 1605-1612, 2014.
APA
Sun, Y., Kumar, P., Sodani, K., Patel, A., Pan, Y., Baer, M.R. ... Jiang, W. (2014). Ponatinib enhances anticancer drug sensitivity in MRP7-overexpressing cells. Oncology Reports, 31, 1605-1612. https://doi.org/10.3892/or.2014.3002
MLA
Sun, Y., Kumar, P., Sodani, K., Patel, A., Pan, Y., Baer, M. R., Chen, Z., Jiang, W."Ponatinib enhances anticancer drug sensitivity in MRP7-overexpressing cells". Oncology Reports 31.4 (2014): 1605-1612.
Chicago
Sun, Y., Kumar, P., Sodani, K., Patel, A., Pan, Y., Baer, M. R., Chen, Z., Jiang, W."Ponatinib enhances anticancer drug sensitivity in MRP7-overexpressing cells". Oncology Reports 31, no. 4 (2014): 1605-1612. https://doi.org/10.3892/or.2014.3002
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