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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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Background/Aims: Thiazolidinediones, which are synthetic insulin sensitizers, are known activators of peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ ligands, including endogenous 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), are thought to elicit antineoplastic effects in various cancer cells. In this study, the antineoplastic effects of PPARγ ligands against hepatocellular carcinoma (HCC) cells were investigated.
Methods: HepG2, Hep3B, and PLC/PRF5 cells were cultured with troglitazone (TGZ), pioglitazone (PGZ), rosiglitazone (RGZ), or 15d-PGJ2 at concentrations of 20-100 μM.. Cell viability, cell cycle arrest, apoptosis, and caspase activity were measured using the MTT assay, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and colorimetric assays, respectively. The effects of various caspase inhibitors were also measured using a cell death detection ELISA.
Results: All three cell lines expressed the PPARγ gene. TGZ and 15d-PGJ2 strongly inhibited growth in HepG2, Hep3B, and PLC/PRF5 cells. In contrast, PGZ and RGZ showed a much weaker effect in all cell lines. In terms of cell cycle arrest and apoptosis, TGZ induced G0/G1 arrest in HepG2 cells and increased the apoptotic fraction in Hep3B and PLC/PRF5 cells. In contrast, 15d-PGJ2 induced apoptosis only in HepG2 and Hep3B cells. TGZ and 15d-PGJ2 increased caspase-3 activity significantly and increased caspase-9 activity slightly. TGZ- and 15d-PGJ2-induced apoptoses were inhibited by a pancaspase inhibitor (Z-VAD-FMK) and a caspase-3 specific inhibitor (Z-DEVD-FMK) in a dose- dependent manner.
Conclusions: TGZ and 15d-PGJ2 elicit antineoplastic effects in various HCC cells via caspase-dependent apoptotic induction. Their differential effects on similar cell types suggest that another antineoplastic mechanism, most likely a PPARγ-independent pathway, is involved. (Korean J Med 75:288-299, 2008)
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참고문헌 (23)
참고문헌 신청
/ / Korea National Statistical Office. The cause of the death
Bae MA / 2003 / Troglitazone but not rosiglitazone induces G1 cell cycle arrest and apoptosis in human and rat hepatoma cell lines / Toxicol Lett 139 : 67 ~ 75
Clay CE / 1999 / Influence of J series prostaglandins on apoptosis and tumorigenesis of breast cancer cells / Carcinogenesis 20 : 1905 ~ 1911
El-Serag HB / 2001 / Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States / Hepatology 33 : 62 ~ 65
Frohlich E / 2005 / Action of thiazolidinediones on differentiation, proliferation and apoptosis of normal and transformed thyrocytes in culture / Endocr Relat Cancer 12 : 29
Bae MA / 2003 / Troglitazone but not rosiglitazone induces G1 cell cycle arrest and apoptosis in human and rat hepatoma cell lines / Toxicol Lett 139 : 67 ~ 75
Clay CE / 1999 / Influence of J series prostaglandins on apoptosis and tumorigenesis of breast cancer cells / Carcinogenesis 20 : 1905 ~ 1911
El-Serag HB / 2001 / Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States / Hepatology 33 : 62 ~ 65
Frohlich E / 2005 / Action of thiazolidinediones on differentiation, proliferation and apoptosis of normal and transformed thyrocytes in culture / Endocr Relat Cancer 12 : 29
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