| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| 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.
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