Apoptosis inhibitors in human hepatocellular carcinomas

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12670478
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Mie University
• Principal Investigator: SHIRAKI Katsuya Mie University, Hospital, Assistant Professor, 医学部・附属病院, 講師 (90263003)
• Co-Investigator(Kenkyū-buntansha): ITO Masaaki Mie University, Hospital, Assistant Professor, 医学部・附属病院, 講師 (00223181)
• Project Period (FY): 2000 – 2001
• Keywords: Apoptosis / Caspase / hepatoma

Research Abstract

PPARγ is known to induce apoptosis in malignant tumor cells, but the mechanism of this induction is not well understood. We investigated induction of apoptosis with 15-Deoxy-Δ^<12,14>-prostaglandin J_2 (15d-PGJ_2), a PPARγ ligand, in cholangio cell carcinoma (CCC) cells (RBE, ETK-1 or HuCCT-1). Apoptosis was induced in RBE and ETK-1 cells with 15d-PGJ_2, but not in HuCCT-1 cells, although PPARγ was expressed in all CCC cells. Apoptosis-related proteins were also expressed, including FLIP, bclx, Apaf-1 and XIAP, but expression levels differed among the three cell lines. RBE cells treated with 15d-PGJ_2 showed caspase activation, and it appeared that PPARγ-induced apoptosis was dependent on caspase activation. However, neither ETK- 1 nor HuCCT-1 cells showed significant activation of caspase-8 or -3 with 15d-PGJ_2 treatment, raising the possibility of a caspase-independent apoptosis induction pathway. XIAP was down-regulated by 15d-PGJ_2 in all three CCC cell lines.
Therefore, 15d-PGJ_2 induces apoptosis in CCC cells via caspase-dependent or independent pathways. 15d-PGJ_2 may also induce down-regulation of XIAP and may promote caspase cascade activation through TNF-family receptor signaling pathways.