Antineoplastic effect of endogenous peroxisome proliferator-activated receptor gamma ligand, 15-deoxy-delta(12,14)-prostaglandin J2, on cholangiocarcinoma cells / 대한내과학회지

ABSTRACT

BACKGROUND/AIMS: Peroxisome proliferator-activated receptor (PPAR)-gamma ligand is known to inhibit the growth of several kinds of cancer cells, yet its effect on cholangiocarcinoma is indecisive. We investigated the effect of an endogenous ligand of PPAR-gamma, 15-deoxy-delta (12,14)-prostaglandin J2 (15-deoxy-PGJ2) on cholangiocarcinoma cells that were established from intrahepatic cholangiocarcinoma tissue of Korean patients. METHODS: Four cholangiocarcinoma cell lines, Cho-CK, Choi-CK, JCK and SCK, were studied. The mRNA expression of PPAR-gamma, bcl-2, and bax were examined by RT-PCR. Cell viability was determined by MTT assay. The cell cycle was analyzed by flow cytometry, and apoptosis by cell death detection ELISA kit. Caspase activity was measured by colorimetric assay. The effect of caspase inhibitors on 15-deoxy-PGJ2-induced apoptosis was determined by measuring cell viability using the MTT assay. RESULTS: PPAR-gamma mRNA was expressed in all cholangiocarcinoma cells. 15-deoxy-PGJ2 inhibited proliferation of all cells in a dose- and time-dependent manner. All cells treated with 15-deoxy-PGJ2 showed increased dose-dependent apoptosis. Caspase 3 was activated in all cells and caspase 9 was activated in all but JCK cells after 15-deoxy-PGJ2 treatment. Caspase 8 activity showed no significant change. The pan-caspase inhibitor, Z-VAD-FMK, and the caspase-3 inhibitor, Z-DEVD-FMK, blocked 15-deoxy-PGJ2-induced apoptosis in all cells dose-dependently. The expression of bcl-2 was decreased in Cho-CK, Choi-CK and SCK cells, and bax expression was not changed significantly after 15-deoxy-PGJ2 treatment. CONCLUSIONS: PPAR-gamma mRNA was expressed in all Korean cholangiocarcinoma cells. Our data suggest that 15-deoxy-PGJ2 exerts an antineoplastic effect against cholangiocarcinoma cells by inducing apoptosis through caspase activation.