KAMIJO Ryutaro Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (70233939)
IWASE Masayasu Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (50193743)
|Budget Amount *help
¥11,000,000 (Direct Cost : ¥11,000,000)
Fiscal Year 1998 : ¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1997 : ¥8,000,000 (Direct Cost : ¥8,000,000)
We investigated the effects of anti-cancer drugs (CDDP, 5-Fu) , IFN-y or NO donors(SNP, SNAP, NOC) on induction of apoptosis mainly in NA cells which had been established from a squamous cell carcinoma of the tongue. Further the effects of these agents on the expression of c-myc and c-myb, adhesion molecules including ICAM-1, Fas/Fas ligand, and soluble Fas were also studied in NA cells. The results obtained were as follows :
1. When NA cells were treated with NO donors, apoptosis of NA cells was induced together with the inhibition of the expression of c-myc and c-myb mRNA.
2. CDDP and 5-Eu induced apoptosis of NA cells and it was suggested that FLICE (caspase 8) might be concerned in the induction of apoptosis of NA cells. However, synergistic -effect was not observed when NA cells were treated both with these anti-cancer drugs.
3. ICAM-1 expression on NA cells was enhanced by the treatment of CDDP or 5- Eu, and simultaneous treatment with CDDP and 5-Eu exhibited synergistic effect on the induction of ICAM-1.
4. Apoptosis was induced when NA cells were treated with IEN-gamma or anti-Fas antibody (CH11). Then, membrane binding Fas was not altered, whereas soluble Eas in the medium was decreased.
5. The expression of Fas and Fas ligand on HL-60 cells, a leukemia cell line, was enhanced by the treatment with IEN-gamma or TNF-alpha, while the expression of bcl-2 protein and its mRNA was reduced by the treatment.
These results indicate that apoptosis is induced both by anti-cancer drugs or NO donors and that the induction of apoptosis is enhanced by IFN-gamma or TNF-alpha.