Radixin knockdown improves the accumulation and efficiency of methotrexate in tumor cells

  • Authors:
    • Atsushi Kawase
    • Yuta Inoue
    • Sayaka Nakazaki
    • Erika Koizumi
    • Masahiro Iwaki
  • View Affiliations

  • Published online on: May 15, 2019     https://doi.org/10.3892/or.2019.7162
  • Pages: 283-290
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Abstract

The plasma membrane localization of efflux transporters, such as multidrug resistance‑associated protein (MRP/ABCC), is governed by scaffold proteins, such as the ezrin/radixin/moesin (ERM) proteins. Reduction of the anchor function of ERM proteins in tumor cells may decrease the transport activity of efflux transporters, possibly leading to increased intracellular accumulation and efficiency of anticancer drugs as substrates of efflux transporters. The effect of the knockdown of ERM proteins was examined in multiple carcinoma cell lines on the transport activity of efflux transporters and on the intracellular accumulation and efficiency of methotrexate (MTX). Radixin knockdown in human liver cancer HepG2 cells, human lung carcinoma A549 cells, and human breast carcinoma MDA‑MB‑453 cells led to a significant reduction in the transport activity of multidrug resistance‑associated protein 2 (MRP2). The plasma membrane localization of MRP2 was significantly decreased by radixin knockdown in HepG2 cells. Increases in the accumulation and cytotoxicity of MTX in HepG2 cells treated with siRadixin were observed compared with control or siNegative. An in vivo study revealed that siRadixin treatment improved the efficiency of MTX in tumor‑bearing mice. In conclusion, the present study provides information on radixin as a target molecule for the modulation of MRP activity in tumor cells.
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July-2019
Volume 42 Issue 1

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

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Spandidos Publications style
Kawase A, Inoue Y, Nakazaki S, Koizumi E and Iwaki M: Radixin knockdown improves the accumulation and efficiency of methotrexate in tumor cells. Oncol Rep 42: 283-290, 2019.
APA
Kawase, A., Inoue, Y., Nakazaki, S., Koizumi, E., & Iwaki, M. (2019). Radixin knockdown improves the accumulation and efficiency of methotrexate in tumor cells. Oncology Reports, 42, 283-290. https://doi.org/10.3892/or.2019.7162
MLA
Kawase, A., Inoue, Y., Nakazaki, S., Koizumi, E., Iwaki, M."Radixin knockdown improves the accumulation and efficiency of methotrexate in tumor cells". Oncology Reports 42.1 (2019): 283-290.
Chicago
Kawase, A., Inoue, Y., Nakazaki, S., Koizumi, E., Iwaki, M."Radixin knockdown improves the accumulation and efficiency of methotrexate in tumor cells". Oncology Reports 42, no. 1 (2019): 283-290. https://doi.org/10.3892/or.2019.7162