Investigation of multidrug resistance in cultured human renal cell carcinoma cells by 31P-NMR spectroscopy and treatment survival assays.
KTCTL-26 and KTCTL-2 are renal cell carcinoma (RCC) lines with high and low expression 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-alpha (IFN-alpha). 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 0.011 mircroM VBL alone (87% vs. 102% survival) or to 0.011 microM BL + 10 microM 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.
Lutz
N W
NW
Central Spectroscopy Department, German Cancer Research Center (DKFZ), Heidelberg, Germany. Lutz@ipb.u-strasbg.fr
Franks
S E
SE
Frank
M H
MH
Pomer
S
S
Hull
W E
WE
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004110:Diltiazem / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010710:Phosphates / Q000032:analysis; D010759:Phosphorus Isotopes; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
D016898:Interferon-alpha; D010710:Phosphates; D010759:Phosphorus Isotopes; D014747:Vinblastine; D004110:Diltiazem