leukotriene-c4 and Adenocarcinoma

ONO-1078 is a new class of peptide leukotriene receptor antagonist, and multidrug resistance protein (MRP) is a membrane tranporter of multiple anticancer drugs and endogenous leukotriene C4 (LTC4). We investigated the effects of ONO-1078 on drug sensitivity and LTC4-efflux in MRP-expressing lung cancer cells. Drug sensitivity, intracellular vincristine accumulation, and intracellular and extracellular LTC4 concentrations were measured with or without ONO-1078. The effect of ONO-1078 on MRP-mediated calcein-efflux was determined by flow cytometry. ONO-1078 (1 to 10 microM) dose-dependently enhanced the sensitivity of NCI-H520 cells to vincristine with the reduced accumulation, and also enhanced the sensitivity to doxorubicin and etoposide. ONO-1078 inhibited both LTC4- and calcein-efflux from the cells with increased intracellular accumulations. Our findings indicate that ONO-1078 modulates multidrug resistance and inhibits LTC4-efflux in lung cancer cells, by inhibition of MRP function.

Topics: Adenocarcinoma; ATP-Binding Cassette Transporters; Carcinoma, Squamous Cell; Chromones; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Flow Cytometry; Fluoresceins; Fluorescent Dyes; Humans; Leukotriene Antagonists; Leukotriene C4; Lung Neoplasms; Multidrug Resistance-Associated Proteins; Tumor Cells, Cultured; Vincristine