| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Research Abstract |
We examined the apoptosis of tongue carcinoma and the effects of anticancer drugs to identify the molecules that mediate apoptotic cascade in the malignancy. Carboplatin (CBDCA), peplomycin and methotrexate induced apoptosis of SCC-25, human well-differentiated tongue squamous carcinoma cell line, as detected by measurement of DNA fragmentation. Neutralizing anti-Fas and anti-Fas ligand (FasL) antibodies obliterated the CBDCA-induced cell death, examined by both measurement of DNA fragmentation and phase-contrast microscopic observation. In the absence of CBDCA, cytotoxic anti-Fas antibody, which binds to and activates Fas at the cell surface, failed to induce the apoptosis. However, the cytotoxic antibody markedly enhanced the CBDCA-induced apoptosis in a dose-dependent manner.
Western blotting and reverse-transcript PCR revealed that there were no alterations in Fas or FasL expression upon CBDCA treatment. SCC-25 induced apoptosis of Jurkat cells, Fas-sensitive T-lymphatic leukemia cell line. These results indicate that the tongue carcinoma cells express nonfunctional Fas and functional Fas ligand, which by themselves fail to induce apoptosis, and that CBDCA treatment switches nonfunctional Fas to functional Fas, activating a Fas sensitive pathway leading to apoptosis.
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