2003 Fiscal Year Final Research Report Summary
Molecular targeting therapy for disseminated ovarian cancer with soluble IGF-IR recombinant protein
| Project/Area Number |
13671719
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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 | Okayama University |
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Principal Investigator |
HONGO Astushi Okayama University, Hospital, Research Associate, 医学部・歯学部附属病院, 助手 (10301293)
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| Co-Investigator(Kenkyū-buntansha) |
KODAMA Junichi Okayama University, Graduate School of Medicine and Dentistry, Associate Professor, 医歯薬学総合研究科, 助教授 (90263582)
YOSHINOUCHI Mituso Okayama University, Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (50261235)
KUDO Takafumi Okayama University, Graduate School of Medicine and Dentistry, Professor, 医歯学総合研究科, 教授 (90127556)
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| Project Period (FY) |
2001 – 2003
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| Keywords | IGF-I Receptor / Ovarian Cancer / Molecular Targeting / Apoptosis / Bystander Effect / Recombinant Protein / 組み換え蛋白 |
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| Research Abstract |
Anti-tumor effects of a soluble form dominant negative of the type I insulin-like growth factor receptor (IGF-IR) designated as 486/STOP were evaluated in CaOV- 3 human ovarian cancer cells by establishing stable transformants overexpressing 486/STOP, and by administration of 486/STOP recombinant protein. Expression of 486/STOP was detected from total cell lysates as well as conditioned media collected from stable transformants. In stable transformants, growth in monolayer was slightly retarded, and anchorage- independent growth in vitro and tumorigenicity in vivo were markedly inhibited. Addition of conditioned media from 486/STOP cells inhibited anchorage-independent growth of parental cells. Although tumorigenicity of parental cells in vivo was abrogated when they were co-cultured in monolayer with 486/STOP cells over 48h prior to injection to nude mice, co-injection of parental cells and 486/STOP cells without pre-culture was not successful. In contrast, administration of 486/STOP partially purified recombinant protein inhibited tumorigenicity of parental cells in vivo. Since 486/STOP cells result in massive apoptosis in vivo within 48h, usage of a recombinant protein has a great advantage to utilize its unique bystander effect in vivo for clinical application.
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