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Investigation of multidrug resistance in cultured human renal cell carcinoma cells by 31P-NMR spectroscopy and treatment survival assays

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Abstract

KTCTL-26 and KTCTL-2 are renal cell carcinoma (RCC) lines with high and lowexpression of P-170 glycoprotein, respectively. Inherent differences between the two cell lines in terms of phosphate metabolites and growth characteristics in culture were examined for possible association with multidrug resistance (MDR). Differences in response to drug treatment were investigated for 40 h incubations with various doses of vinblastine (VBL) alone or as cotreatments with various concentrations of the calcium antagonist diltiazem (DIL) and/or interferon–α (IFN-α). Treatment effects were quantitated using the MTT survival assay and 31P magnetic resonance spectroscopy (MRS) to determine phosphate metabolite profiles in intact cells. KTCTL-2 and KTCTL-26 cells exhibited significant inherent differences in phosphocholine, glycerophosphocholine, glycerophosphoethanolamine, and phosphocreatine levels. KTCTL-26 cells were more sensitive than KTCTL-2 to 0.011μM VBL alone (87% vs. 102% survival) or to 0.011μM BL + 10μM DIL (55% vs. 80% survival). The latter treatment resulted in a significant decrease in the ratio of phosphocholine to glycerophosphocholine in KTCTL-26 cells but no significant changes in phosphate metabolites in KTCTL-2 cells. Metabolomic 31P MRS detects different metabolite profiles for RCC cell lines with different MDR phenotypes and may be useful for noninvasive characterization of tumors in a clinical setting.

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Authors and Affiliations

  1. Central Spectroscopy Department, German Cancer Research Center (DKFZ), Heidelberg, Germany

    N.W. Lutz, S.E. Franks, S. Pomer & W.E. Hull

  2. Department of Urology, University of Heidelberg, Heidelberg, Germany

    M.H. Frank & S. Pomer

  3. Renal Division, Dept. of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    M.H. Frank

  4. Faculté de Médecine, Institut Physique Biologique, Université Louis Pasteur, 4 rue Kirschleger, F-67000, Strasbourg, France

    N.W. Lutz

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  4. S. Pomer
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Lutz, N., Franks, S., Frank, M. et al. Investigation of multidrug resistance in cultured human renal cell carcinoma cells by 31P-NMR spectroscopy and treatment survival assays. MAGMA 18, 144–161 (2005). https://doi.org/10.1007/s10334-005-0107-7

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