| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
TNF-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in various transformed cell lines. Therefore we investigated TRAIL sensitivity, TRAIL-induced NF-xB activation, and the expression of TRAIL in human colonic adenocarcinoma cell lines (HT 29, LS180, SK-CO-1). All four TRAIL receptors (TRAIL-RI-R4) are expressed in these cell lines. TRAIL sensitivity was assessed by assay of cell viability. Cancer cell viabilities were 83±3.1% (HT-29), 90±4.3% (LS180) and 88±6.3% (SK-CO-1) at 24 hours after the addition of 100ng/ml TRAIL, indicating that these cell lines were relatively resistant to TRAIL. Activation of NF-xB was variably influenced by TRAIL administration, with no consistent tendency among the cell lines, indicating that TRAIL-induced NF-xB activation might be cell-type dependent. In contrast, TRAIL was expressed in the human colonic adenocarcinoma cell lines by western blotting and RT-PCR. Increased expression of TRAIL on tumor cells were observed by flow cytometry after cytokine stimulation (IFNγ, TNFα) or the addition of chemotherapeutic agents (camptothecin, doxolubicin hydrochloride). The TRAIL on HT-29 cells was functional and able to induce apoptosis in Jurkat cells. The Jurkat cell viability increased by addition of TRAILR1-R4-Fc. In the presence of various cytokines or existence of chemotherapeutic agents, functional TRAIL is expressed on the surface of tumor cells, and this expressed TRAIL might contribute to tumor immune privilege by inducing apoptosis of activated human lymphocytes.
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