| Project/Area Number |
17591605
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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 |
Orthopaedic surgery
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| Research Institution | Aichi Cancer Center Institution |
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Principal Investigator |
SUGIURA Hideshi Aichi Cancer Center Research Institute, Division of Molecular Pathology, Researcher, 分子病態学部, 研究員 (50303615)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Kenji Aichi Cancer Center Research Institute, Division of Molecular Pathology, Researcher, 分子病態学部, 研究員 (10416167)
TAGUCHI Osamu Aichi Cancer Center Research Institute, Division of Molecular Pathology, Section Head, 分子病態学部, 室長 (00142167)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | osteosarcoma / angiogenesis / LM8 / angiotensin II type 1 / Candesartan / lung metastasis / ACE inhibitor / VEGF / 血管新生抑制 / 腫瘍増殖 / 転移抑制 / angiotensin type1 |
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| Research Abstract |
To determine whether an AT1R antagonist could inhibit osteosarcoma progression and metastasis in vivo, we used mice transplanted with the LM8 cell line. This study used Candesartan as an AT1R antagonist, a drug widely used to treat hypertension. Treatment was initiated one day after tumor cell injection with daily i.p. injections of Candesartan at 0.1mg/kg, 1mg/kg or 10mg/kg or saline (control). The size of subcutaneous tumors and number of lung metastatic colonies was measured after 28 days of treatment. The size of subcutaneous tumors was smaller in the treatment groups than the control group (P=0.05). Significantly fewer lung metastatic colonies were observed in the Candesartan treatment group as compared to the control group. Examination of lung tissue specimens also revealed that pulmonary metastasis was likely to be inhibited in the Candesartan treatment groups when compared to the control group. Candesartan inhibited invasive capacity involved in tumor proliferation, as well as angiogenesis through blocking AT1R-mediated. signaling. Results of this study showed for the first time the cytostatic effects of an AT1R antagonist on tumor proliferation and distant metastasis in a murine osteosarcoma model.
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