Antineoplastic effect of endogenous peroxisome proliferator-activated receptor gamma ligand, 15-deoxy-delta(12,14)-prostaglandin J2, on cholangiocarcinoma cells.
- Author:
Sung Hoon JUNG
1
;
Byung Ho KIM
;
Young Il KIM
;
Jaejun SHIM
;
Young HWANGBO
;
Jae Young JANG
;
Seok Ho DONG
;
Hyo Jong KIM
;
Young Woon CHANG
;
Rin CHANG
;
Dae Ghon KIM
Author Information
1. Department of Internal Medicine, Cheil General Hospital, Kwandong University College of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
PPAR gamma;
15-deoxy-PGJ2;
Cholangiocarcinoma;
Apoptosis
- MeSH:
Amino Acid Chloromethyl Ketones;
Apoptosis;
Caspase 3;
Caspase 8;
Caspase 9;
Caspase Inhibitors;
Cell Cycle;
Cell Death;
Cell Line;
Cell Survival;
Cholangiocarcinoma;
Enzyme-Linked Immunosorbent Assay;
Flow Cytometry;
Liver Neoplasms;
Oligopeptides;
Peroxisomes;
PPAR gamma;
Prostaglandin D2;
RNA, Messenger
- From:Korean Journal of Medicine
2010;78(1):75-86
- CountryRepublic of Korea
- Language:Korean
-
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.
