Different roles for K+ channels in cisplatin-resistant cell lines argue against a critical role for these channels in cisplatin resistance

Xing Jie Liang, Barbara Taylor, Carol Cardarelli, Jun Jie Yin, Jean Philippe Annereau, Susan Garfield, Stephen Wincovitch, Gergely Szakács, Michael M. Gottesman, Adorjan Aszalos

Research output: Article

9 Citations (Scopus)

Abstract

Cisplatin resistance has been associated with altered K+ fluxes. Here, we focused our investigations on the detection of K+ channels in a series of cisplatin-resistant (CP-r) cells with increasing resistance and on the functional relationship of these K+ channels to resistance. Microarray analysis and confocal microscopy indicated that there was overexpression of the ether-a-gogo gene (HERG) and the inwardly rectifying potassium channel gene (TWIK) in a human epidermal KB and human liver BEL-7404 carcinoma cell line series selected for cisplatin resistance. With increased resistance, the plasma membrane potential, but not the mitochondrial membrane potential, also increases in these two series. For these reasons, we conducted cell proliferation studies in the presence of either antibodies directed against the detected K+ channels, omeprazole (a H+ pump inhibitor) or a specific inhibitor of the HERG channel (WAY-123398-A-5). The antibodies and omeprazole influenced cell growth only very slightly. The specific K+ channel blocker did not alter cisplatin resistance. We also observed that manipulation of K+ fluxes with antibodies and the H+ pump with omeprazole resulted in opposite effects on cisplatin resistance in these two cell lines. We conclude that K+ and H + homeostasis are not critical factors in cisplatin resistance since they affect cisplatin resistance differently in KB and BEL-7404 cells.

Original languageEnglish
Pages (from-to)4113-4122
Number of pages10
JournalAnticancer research
Volume25
Issue number6 B
Publication statusPublished - nov. 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Liang, X. J., Taylor, B., Cardarelli, C., Yin, J. J., Annereau, J. P., Garfield, S., Wincovitch, S., Szakács, G., Gottesman, M. M., & Aszalos, A. (2005). Different roles for K+ channels in cisplatin-resistant cell lines argue against a critical role for these channels in cisplatin resistance. Anticancer research, 25(6 B), 4113-4122.