| Project/Area Number |
10671539
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Tottori University School of Medicine |
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Principal Investigator |
KANAMORI Yasunobu (1999-2000) Tottori Univ.Dept.Obstet.Gynecol., Research Associates, 医学部, 助手 (70283984)
皆川 幸久 (1998) 鳥取大学, 医学部, 講師 (70190692)
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| Co-Investigator(Kenkyū-buntansha) |
TERAKAWA Naoki Tottori Univ.Dept.Obstet.Gynecol., Professor, 医学部, 教授 (90163906)
KIGAWA Junzo Tottori Univ.Dept.Obstet.Gynecol., Assistant Professor, 医学部, 助教授 (00177784)
金森 康展 鳥取大学, 医学部, 助手 (70283984)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Ovarian cancer / Apoptosis / Chemosensitivity / Cisplatin / p53 |
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| Research Abstract |
1. The effect of p53 gene transduction to chemosensitivity.
(1) p53 gene transduction by the recombinant adenovirus vector (AxCAp53) suppressed the cell growth and increased chemosensitivity to CDDP in SK-OV-3 and HeLa cells without p53 function. In contrast, AxCAp53 transfection did not affect the cell growth and the chemosensitivity in CDDP-resistant HeLa (HeLa/CDDP) cells.(2) Chemosensitivity to paclitaxel (PTX) was not affected by AxCAp53 in SK-OV-3, HeLa and HeLa/CDDP cells.(3) In SCID mice implanted with SK-OV-3 cells, the combination treatment of AxCAp53 and CDDP significantly inhibited the tumor growth, and increased Bax expression in tumors.
2. Induction of apoptosis and action of apoptotic pathway by the combination treatment of AxCAp53 and CDDP.
(1) AxCAp53 transfection or exposure to CDDP produced DNA fragmentation in SK-OV-3 and HeLa cells. The combination treatment of AxCAp53 and CDDP enhanced DNA fragmentation and increased Bax expression in those cells. DNA fragmentation did not appear after AxCAp53 transfection or exposure to CDDP in HeLa/CDDP cells. The combination treatment of AxCAp53 and CDDP did not affect DNA fragmentation and Bax expression.(2) PTX-induced DNA fragmentation and Bax expression did not change after the combination treatment of AxCAp53 and PTX.
The present study suggests that CDDP-resistant cells have a phenotype that is resistant to p53-dependent and-independent apoptosis and that PTX may induce p53-independent apoptosis.
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