Abstract
cis-Diamminedichloroplatinum (II) (CDDP) is one of most active anticancer agents for lung cancer. In this study, we evaluated the role of thromboxane A2 (TXA2), a metabolite of arachidonate, as a determinant of sensitivity to CDDP in non-small cell lung cancer (NSCLC) cell lines <i>in vitro</i> by using selective TXA2 receptor antagonists, S-1452 and BAYu3405. A-549, EBC-1, PC-3, and RERF-LC-MS cell lines which had been derived from human NSCLC were used for these experiments. Drug sensitivity tests were performed with MTT-assay. IC50 values for CDDP and an analogue (CBDCA) of these cell lines by 2-hour exposure were decreased by co-incubation with these TXA2 antagonists. Cellular accumulation of CDDP and CBDCA increased by S-1452. These results indicate the important role of endogenous TXA2 to modulate the cellular accumulation of the platinum agents and to determine intrinsic resistance to these agents in NSCLC cell lines.
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