127 Modulation of cis-diamminedichrolo-platinum (II) sensitivity by a thromoboxane A2 receptor antagonist in non-small cell lung cancer cell lines

Abstract

We evaluated the effect of thromboxane A2 (TXA2) receptor antagonists, calcium 5 (Z)-IR, 2S, 3S, 4S-7-[3-phenylsulfonylamidnobicyclo [2.2.1] hept-2-yl]-5-heptonoate hydrate (S-1452) on cis-diamminedichrolo-platinum (II) (CDDP) sensitivity in PC-9, a non small cell lung cancer (NSCLC) cell line, and PC-9/CDDP (6.0-fold resistant to CDDP) in vitro . In PC-9 cells, treatment with 250 or 500 μM of S-1452 caused 2. I fold and 4.6-fold increase in IC50 values, respectively. In PC-9/CDDP cells, treatment caused 3. I fold and 6.0 fold increase in IC50 values. Glutathione contents and glutathione S-transferase activities of these cell lines were not affected by treatment with S-1452. Uptake of CDDP after 2 h drug exposure into PC-9 was l.3-fold increased by treatment with 500 μM of S-1452 and that into PC-9/CDDP was 1.4-fold increased. These results suggest that TXA2 receptor might be related with sensitivity to CDDP in NSCLC cell lines and increase in CDDP uptake might contribute to the sensitizing effect of S-1452.