The overexpression of multidrug resistance-associated proteins and gankyrin contribute to arsenic trioxide resistance in liver and gastric cancer cells

  • Authors:
    • Xi Chen
    • Mu Zhang
    • Lian-Xin Liu
  • View Affiliations

  • Published online on: July 1, 2009     https://doi.org/10.3892/or_00000408
  • Pages: 73-80
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Abstract

Arsenic trioxide has been used as a therapeutic agent for acute promyelocytic leukemia and recently for some solid tumors. Although arsenic trioxide has been shown to significantly inhibit the growth of solid tumor cells in vitro, clinical trials indicate that arsenic trioxide alone is pool active against non-hematologic malignant diseases. To understand the mechanisms of arsenic resistance in solid tumor cells, we established two arsenic-resistant solid tumor cell lines, HepG2/AS and SGC7901/AS, isolated from human liver cancer cell line HepG2 and human gastric cancer cell line SGC7901, respectively, by a series of stepwise selections via treatment with increasing concentrations of arsenic trioxide. Three ABC transporter proteins, ABCB1, ABCC1 and ABCC2, were expressed increasingly and differently in two arsenic-resistant cell lines. Further, tumor suppressor p53 was overexpressed in two arsenic-resistant cell lines, but the levels of p53 mediators MDM2 and gankyrin, which regulate the ubiquitination of p53, increased simultaneously. In addition, an increase in the phosphorylation of Rb at Ser795 in the two cell lines might also result from the presence of MDM2 and gankyrin, which suggest that the inactivation of p53 and Rb contribute to drug resistance. These two arsenic-resistant solid tumor cell lines, HepG2/AS and SGC7901/AS, may be useful for studying the mechanism of arsenic resistance in solid tumors and may provide a way to overcome it.

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July 2009
Volume 22 Issue 1

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

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Spandidos Publications style
Chen X, Zhang M and Liu L: The overexpression of multidrug resistance-associated proteins and gankyrin contribute to arsenic trioxide resistance in liver and gastric cancer cells. Oncol Rep 22: 73-80, 2009
APA
Chen, X., Zhang, M., & Liu, L. (2009). The overexpression of multidrug resistance-associated proteins and gankyrin contribute to arsenic trioxide resistance in liver and gastric cancer cells. Oncology Reports, 22, 73-80. https://doi.org/10.3892/or_00000408
MLA
Chen, X., Zhang, M., Liu, L."The overexpression of multidrug resistance-associated proteins and gankyrin contribute to arsenic trioxide resistance in liver and gastric cancer cells". Oncology Reports 22.1 (2009): 73-80.
Chicago
Chen, X., Zhang, M., Liu, L."The overexpression of multidrug resistance-associated proteins and gankyrin contribute to arsenic trioxide resistance in liver and gastric cancer cells". Oncology Reports 22, no. 1 (2009): 73-80. https://doi.org/10.3892/or_00000408