| Antineoplastic effect of endogenous peroxisome proliferator-activated receptor γ ligand, 15-deoxy-delta(12,14)-prostaglandin J2, on cholangiocarcinoma cells |
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Sung Hoon Jung, 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 |
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| 담관암세포주에서 내인성 peroxisome proliferator-activated receptor gamma 배위자인 15-deoxy-delta(12,14)-prostaglandin J2의 항암 효과 |
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정성훈·김병호·김영일·심재준·황보영·장재영, 동석호·김효종·장영운·장 린·김대곤, Young Il Kim, Jaejun Shim, Young Hwangbo, Jae Young Jang, Seok Ho Dong, Hyo Jong Kim, Young Woon Chang, Rin Chang, Dae-Ghon Kim |
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| Abstract |
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Background/Aims: Peroxisome proliferator-activated receptor (PPAR)-γ 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-γ,
15-deoxy-δ (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-γ, 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-γ 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-γ 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. (Korean J Med
78:75-86, 2010) |
| Key Words:
PPAR gamma; 15-deoxy-PGJ2; Cholangiocarcinoma; Apoptosis |
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