| Project/Area Number |
06671642
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nagoya University |
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Principal Investigator |
GOTO Setsuko Nagoya Univ., College of medical Technology, Professor, 医療技術短期大学部, 教授 (80111847)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Noriko Nagoya Univ., School of Med., Medical Staff (Senior Resident), 医学部, 医員
WAKAHARA Yasunori Nagoya Univ., School of Med., Medical Staff (Senior Resident), 医学部, 医員
SUZUKI Takanobu Nagoya Univ., School of Med., Medical Staff (Senior Resident), 医学部, 医員
INO Kazuhiko Nagoya Univ., School of Med., Medical Staff (Senior Resident), 医学部, 医員
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Ubenimex (bestatin) / cell-growth suppression / aminopeptidase N / Monoclonal antibody / Immunoblotting / MTT assay / bestatin uptake / flow cytometry / DNAhistogram / アミノペプチダーゼN / MMT assay |
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| Research Abstract |
We previously found that ubenimex (bestatin), an aminopeptidase inhibitor, had a growth-suppressive effect on cancer cells. To clarify the mechanism of the growth-suppressive effect, we investigated the expression of aminopeptidase N (AP-N/CD13) on choriocarcinoma cells and other human tumor cells.
1) Two choriocarcinoma cell lines, NaUCC-4 and BeWo, had higher AP-N activity than other cell lines, as did the human myeloid leukemia cell line, IIL-60.2) These choriocarcinoma and leukemia cell lines with aboundunt AP-N activity showed much higher sensitivity to bestatin than the other cell lines. 3) By immunoblotting and immunocytochemical staining, AP-N was detected as an approximately 165-kDa protein and localized on the cell membrane in choriocarcinoma cells. 4) We examined the effects of three anti-CD13 monoclonal antibodies (WM15, MCS2, and MY7) on the growth of NaUCC-4 cells. Of the three MABs, only WM15, which is able to inhibit AP-N activity, suppressed cell growth in a dose-dependent manner.
These results indicate that AP-N inhibitors show a growth-suppressive effect, presumably through inhibition of the enzyme activity of AP-N on carcinoma cells.
5) we examined bestatin uptake using 3H-bestatin in choriocarcinoma cells and other cells. A higher upake of 3H-bestatin was resulted in NaUCC-4 cells, which showed the highest sensitivity bestatin. 6) In DNA histogram, NaUCC-4 cells treated with bestatin were not blocked at any cell-cycle phases as studied by flow fluorocytometry.
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