2005 Fiscal Year Final Research Report Summary
Anti-tumor effects of angiotensin II type 1 antagonist in hormone-refractory prostate cancer.
| Project/Area Number |
16591621
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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 |
Urology
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| Research Institution | Keio University |
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Principal Investigator |
MIYAJIMA Akira Keio University, School of Medicine, Instructor, 医学部, 助手 (90245572)
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| Co-Investigator(Kenkyū-buntansha) |
KOSUGI Michio Keio University, School of Medicine, Instructor, 医学部, 助手 (10317216)
NAKASHIMA Jun Keio University, School of Medicine, Associate Professor, 医学部, 助教授 (10167546)
MURAI Masaru Keio University, School of Medicine, Professor, 医学部, 教授 (90101956)
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| Project Period (FY) |
2004 – 2005
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| Keywords | prostate cancer / hormone-refractory / angiotensin II / angiogenesis |
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| Research Abstract |
We first determined whether hormone-independence is associated with tumor angiogenesis and AT1R expression. Accordingly, we postulated that AT1R blockade may affect angiogenesis in androgen-independent PCa rather than in androgen-dependent Pca, and investigated the effects of AII and candesartan on PCa cell lines and a tumor xenograft model.
A human hormone-refractory PCa (HRPC) and C4-2 androgen-independent PCa cell line showed significantly higher expression of VEGF, MVD, and AT1R than did human androgen-dependent PCa and an LNCaP androgen-dependent PCa cell line. In vitro, AII and candesartan did not directly affect the proliferation of LNCaP and C4-2 cells, but candesartan significantly suppressed VEGF production in C4-2 cells. In vivo, candesartan significantly suppressed VEGF expression, serum PSA concentration and tumor growth (1.1±0.2, 45.0±17.6ng/ml, 235.8±37.4mm3) in C4-2 xenografts in castrated mice, compared with the controls (2.4±0.6, 376.7±74.2ng/ml, 830.8±147.6mm3).
We nest investigated the effects of candesartan in bladder cancer xenograft model, and found similar results in bladder cancer model.
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