The role of laminin-peptide for overian cancer
| Project/Area Number |
16591650
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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 | University of Fukui |
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Principal Investigator |
YOSHIDA Yoshio University of Fukui, University of Fukui Hospital, Lecturer, 医学部附属病院, 講師 (60220688)
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| Co-Investigator(Kenkyū-buntansha) |
KUROKAWA Tetsuji University of Fukui, Faculty of Medical Sciences, Assistant Professor, 医学部, 助手 (60334835)
YAGIHARA Akira University of Fukui, University of Fukui Hospital, M.D., 医学部附属病院, 医員 (00402016)
KOTSUJI Fumikazu University of Fukui, Faculty of Medical Sciences, Professor, 医学部, 教授 (50153573)
河原 和美 福井大学, 医学部附属病院, 助手 (60234100)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | ovarian cancer / metastasis / Laminin peptide / PI3K / AKT / ラミニンペプタイド / 浮遊細胞 |
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| Research Abstract |
Cisplatin is one of the most potent antitumor agents in ovarian cancer, although it is implicated in cytotoxicity in normal tissue. We have examined the effect of cisplatin alone and in combination with C16Y, which has been identified new anti-angiogenic peptide from NH2-terminal domains of the γ chain of laminin-1, on modulation of Bcl-2/Bax expression and induction of apoptosis in OVACAR 3 ovarian cancer cells. C16Y dose not elicit any cell death on human umbilical vein endothelial cells (HUVEC). Cisplatin exerted its lethal effect with an EC50 of 10〓M. In the presence of 10 or 25μg/ml of C16Y (in the range used no effect against HUVEC), the EC50 for cisplatin was reduced to 3.5μM or 2.0μM, respectively. Using fluorescence-activated cell sorting (FACS) analysis of DNA stained cells and terminal deoxynucleotide tranferase-mediated dUTP nick end labeling (TUNEL) method, we found that even at concentrations of 1μM and 3μM cisplatin, C16Y at 50 and 150 μγ/ml increased the incidence of apoptosis in these cells by 3-5 fold. Each drugs had some measurable effect on Bax protein expression. Furthermore, Bcl-2 protein expression levels were markedly reduced by C16Y and cisplatin in a dose dependent manner. The combination of C16Y and cisplatin resulted in a further dramatic reduction in Bcl-2, underscoring the pronounced synergy of cisplatin and C16Y. On the other hand, C16Y did not activate any another signal transduction pathways, which culminated in the activation of apoptosis, such as p53, p21, p73, MAPK, and P13-AKT pathways. These observations suggest that suppression of Bcl-2/Bax ratios may play an important role in mediating the synergistic effect of cisplatin and C16Y on induction of apoptosis in ovarian cancer cells.
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Report
(3 results)
Research Products
(11 results)
