| Project/Area Number |
07457491
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Kochi Medical School |
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Principal Investigator |
OSAKI Tokio Kochi Medical School, Department of Oral Surgery, Professor, 医学部, 教授 (70031995)
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| Co-Investigator(Kenkyū-buntansha) |
UETA Eisaku Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部・附属病院, 助手 (10203431)
YAMAMOTO Tetsuya Kochi Medical School, Department of Oral Surgery, Assistant Professor, 医学部・附属病院, 講師 (00200824)
YONEDA Kazunori Kochi Medical School, Department of Oral Surgery, Associate Professor, 理学部, 助教授 (90182849)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | squamous cell carcinoma cells / apoptosis / p53 / TGF-beta / 5-FU / gamma-rays / p21 / cyclin-dependent kinase / 扁平上皮癌 |
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| Research Abstract |
We examined differentiation and apoptosis in both p53-wild type and p53-mutant type squamous cell carcinoma cell (SCC) lines and obtained the following results.
1. Differentiation was induced in all cell lines by vesnarinone (a differentiation inducer), 5-FU, TGF-beta and gamma-rays. p21 anti-sense inhibited vesnarinone- and TGF-beta-induced differentiation. Apoptosis was induced by peplomycin, 5-FU and gamma-rays although only weakly induced by TGF-beta and not induced by vesnarinone.
2. Accumulation of SCCs in the G1, S and G2/M phase was induced by vesnarinone, 5-FU and gamma-rays, respectively. However, the expression of cyclin D and E, Cdk2 and 4 was not changed by these reagents.
3. The p21-promoter activity was upregulated by TGF-beta in all cell lines but suppressed by other reagents. The p21 protein expression was increased by TGF-beta and vesnarinone (vesnarinone possessed a p21-mRNA-stabilizing activity) but 5-FU, peplomycin and gamma-rays suppressed the expression of p21.
4. By combinations of IL-2-induced cytotoxic lymphocytes and gamma-rays, 5-FU or others, apoptosis was more strongly induced.
5. Mn-SOD activity was inversely correlated with the induction of apoptosis. SCCs which possessed low level Mn-SOD activities more strongly fell into apoptosis than those with high Mn-SOD activities. Mn-SOD was also inversely associated with decrease of the potential (psi) of mitochondrial membrane and cleavage of caspase-3 and PARP.
These results indicate that however vesnarinone and TGF-beta induced differentiation in a p21-dependent manner, gamma-rays and 5-FU induce differentiation and apoptosis in p53- and p21-independent manners accumulating SCCs in the cell phase specific for each inducer, that combinations of cytotoxic lymphocytes and anticaner agents are useful for induction of apoptosis and that suppression of Mn-SOD activity is beneficial to induction of apoptosis in SCCs.
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