Clofibric Acid, a Peroxisome Proliferator-activated Receptor Alpha Ligand, Enhances a Suppressive Effect of Cis-diaminedichloroplatinum on Proliferation of Ovarian Carcinoma Cells

Abstract

Abstract:The purpose of this study was to elucidate the possible mechanism that clofi bric acid (CA), a peroxisome proliferator-activated receptor α ligand, enhances a suppressive effect of cis-diaminedichloroplatinum (CDDP) on proliferation of the ovarian carcinoma line OVCAR-3. These cells was incubated with 0.5 µM/ml CDDP in the presence or absence of 50 µM CA or incubated with 50 µM CA alone for 72 hr. While treatment with CA alone did not affect proliferation of OVCAR-3 cells, simultaneous treatment with CDDP and CA signifi cantly suppressed proliferation of the cells and significantly induced apoptosis compared to that with CDDP alone. Treatment with CDDP and CA signifi cantly decreased the prostaglandin (PG) E 2 level in the medium of the cells compared with treatment with CDDP alone. These results suggest the ability of CA to enhance a suppressive effect of CDDP on proliferation of the ovarian carcinoma cells through reduction of PGE 2 level.

Combination of ciglitazone, a peroxisome proliferator-activated receptor gamma ligand, and cisplatin enhances the inhibition of growth of human ovarian cancers

“…In our previous study, although clofibric acid (CA), PPARa ligand, alone did not affect proliferation of ovarian cancer cells, simultaneous treatment with cisplatin and CA significantly suppressed proliferation of the cells compared with that with cisplatin alone and treatment with cisplatin in the presence of CA significantly increased the number of apoptotic cells compared with that with cisplatin alone (Yokoyama et al 2007b). CA reduced PGE 2 level in the culture medium, and as a result, the decrease in PGE 2 level might enhance the ability of cisplatin to induce apoptosis and anti-angiogenesis (Yokoyama et al 2007b). Thus, because ciglitazone alone significantly decreased PGE 2 concentration as shown in Fig.…”