Tandutinib (MLN518) reverses multidrug resistance by inhibiting the efflux activity of the multidrug resistance protein 7 (ABCC10)

  • Authors:
    • Wen Deng
    • Chun-Ling Dai
    • Jun-Jiang Chen
    • Rishil J. Kathawala
    • Yue-Li Sun
    • Hai-Fan Chen
    • Li-Wu Fu
    • Zhe-Sheng Chen
  • View Affiliations

  • Published online on: March 22, 2013     https://doi.org/10.3892/or.2013.2362
  • Pages: 2479-2485
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

It is well established that ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR) is one of the major mechanisms that causes resistance to antineoplastic drugs in cancer cells. ABC transporters can significantly decrease the intracellular concentration of antineoplastic drugs by increasing their efflux, thereby lowering their cytotoxic activity. One of these transporters, the multidrug resistance protein 7 (MRP7/ABCC10), has already been shown to produce resistance to antineoplastic drugs by increasing the efflux of the drugs. In the present study, we investigated whether tandutinib, an FMS-like tyrosine kinase 3 (FLT3) inhibitor, has the potential to reverse MRP7-mediated MDR. Our results revealed that tandutinib significantly enhanced the sensitivity of MRP7-transfected HEK293 cells to the 2 established MRP7 substrates, paclitaxel and vincristine, whereas there was less or no effect on the control vector-transfected HEK293 cells. [³H]-paclitaxel accumulation and efflux studies demonstrated that tandutinib increased the intracellular accumulation of [³H]-paclitaxel and inhibited the efflux of [³H]-paclitaxel from HEK-MRP7 cells. In addition, western blot analysis showed that tandutinib did not significantly affect MRP7 expression. Thus, we conclude that the FLT3 inhibitor tandutinib can reverse MRP7-mediated MDR through inhibition of the drug efflux function and may have potential to be used clinically in combination therapy for cancer patients.
View Figures
View References

Related Articles

Journal Cover

June 2013
Volume 29 Issue 6

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Deng W, Dai C, Chen J, Kathawala RJ, Sun Y, Chen H, Fu L and Chen Z: Tandutinib (MLN518) reverses multidrug resistance by inhibiting the efflux activity of the multidrug resistance protein 7 (ABCC10). Oncol Rep 29: 2479-2485, 2013.
APA
Deng, W., Dai, C., Chen, J., Kathawala, R.J., Sun, Y., Chen, H. ... Chen, Z. (2013). Tandutinib (MLN518) reverses multidrug resistance by inhibiting the efflux activity of the multidrug resistance protein 7 (ABCC10). Oncology Reports, 29, 2479-2485. https://doi.org/10.3892/or.2013.2362
MLA
Deng, W., Dai, C., Chen, J., Kathawala, R. J., Sun, Y., Chen, H., Fu, L., Chen, Z."Tandutinib (MLN518) reverses multidrug resistance by inhibiting the efflux activity of the multidrug resistance protein 7 (ABCC10)". Oncology Reports 29.6 (2013): 2479-2485.
Chicago
Deng, W., Dai, C., Chen, J., Kathawala, R. J., Sun, Y., Chen, H., Fu, L., Chen, Z."Tandutinib (MLN518) reverses multidrug resistance by inhibiting the efflux activity of the multidrug resistance protein 7 (ABCC10)". Oncology Reports 29, no. 6 (2013): 2479-2485. https://doi.org/10.3892/or.2013.2362