Project/Area Number |
13671986
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
病態科学系歯学(含放射線系歯学)
|
Research Institution | KANAZAWA MEDICAL UNIVERSITY |
Principal Investigator |
TANAKA Takuji Kanazawa Medical University, Dept. Pathol., Professor, 医学部, 教授 (40126743)
|
Co-Investigator(Kenkyū-buntansha) |
TOIDA Makoto Gifu Univ. Sch. Med., Dept., Assistant Prof., 医学部, 助手 (90313890)
KOHNO Hiroyuki Kanazawa Medical University, Dept. Pathol., Lecturer, 医学部, 講師 (20221236)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | PPAR / Ligand / Tongue carcinogenesis / 4-NQO / Chemoprevention / Rats / 発がん防御 / 舌がん培養株 / 増殖抑制 / 細胞周期修飾 / アポトーシス |
Research Abstract |
The present study was conducted to investigate the possible involvement of PPAR expression during tongue carcinogenesis and the chemopreventive ability of PPAR ligands against tongue tumorigenesis in rats. The results obtained are as follows : 1) The human tongue cancer cell lines HCS-2 and NA expressed PPARγ and the expression of NA was greater than HCS-2. 2) The growth of HCS-2 was inhibited by adding at high doses (40-50 μM) of a PPARγ ligand troglitazone and that of NA was inhibited dose-dependently by adding of troglitazone. FCM analysis revealed that troglitazone caused G1 arrest and apoptosis in both cell lines. The treatment also induced COX-2 expression. 3) Dietary troglitazone (100 ppm) significantly inhibited 4-NQO-induced rat tongue carcinogenesis. 4) Rat tongue squamous cell carcinoma induced by 4-NQO did not have β-catenin mutation. 5) Dietary silymarin, which is an antioxidant and an inhibitor of arachidonic acid cascade, inhibited 4-NQO-induced rat tongue carcinogenesis through inhibition of cell proliferation and PGE2 biosynthesis. 6) Apoptosis inducers capsaicin and rotenone from plants inhibited 4-NQO-induced rat tongue carcinogenesis through inhibition of cell proliferation and induction of Phase II drug metabolizing enzymes.
|