| Project/Area Number |
11670561
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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 |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
WATANABE Akira Institute of Development, Aging, and Cancer, Tohoku University, Associated Professor, 加齢医学研究所, 助教授 (70220861)
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| Co-Investigator(Kenkyū-buntansha) |
MUNAKATA Hiroshi Kinki University, School of Medicine, Professor, 医学部, 教授 (90111294)
NARUMI Ko Tohoku University Hospital, Assistant Professor, 医学部・附属病院, 助手 (30302219)
EBINA Masahito Tohoku University Hospital, Assistant Professor, 医学部・附属病院, 助手 (10280885)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Decorin / Lung Cancer / Gene Therapy / Adenovirus vector |
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| Research Abstract |
Decorin is a member of the small leucine-rich proteoglycan gene family that has recently become a focus in various areas of cell biology, e. g. cell attachment, migration, and proliferation. The decorin protein consists of a core protein and a covalently linked glycosaminoglycan chain. Decorin binds to transforming growth factor-beta (TGF-beta), and inhibit the function. TGF-beta is released by various types of tumors and may promote immunosuppression in the host, may modulate tumor growth, may mediate drug resistance, and may facilitate tumor angiogenesis. Furthermore, decorin suppresses the cell cycle via the induction of p21WAF1/CIP1 (p21), a inhibitor of cyclin-dependent kinase. On the basis of these knowledge, we hypothesized a potential inhibition of tumor growth by adenoviral-mediated decorin gene transfer in vivo, and constructed an adenoviral vector encoding decorin driven by CMV promoter (Ad-DC). Although in vitro infection of A549 cells with the Ad-DC vector yielded decorin mRNA transcripts, cell growth rate was not altered compared to control cells infected with control vector (AdNull). Direct injections of Ad-DC (1 x 10^9 pfu) at day 1 and day 10 into established subcutaneous tumors of A549 in BALB/c nude mice resulted in reduction in tumor growth by 23.3% at 3 weeks compared with AdNull injection, however, there was no significance (n=4, p=0.19). These results indicate that while decorin transduction did not affect the growth of lung cancer cells in vitro and in vivo. In the next step, we should apply Ad-DC vector to other cancer cell lines.
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