| Project/Area Number |
16591491
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
SHIMOSE Shouji Hiroshima University, Hospital, Assistant, 病院, 助手 (30304439)
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| Co-Investigator(Kenkyū-buntansha) |
OCHI Mitsuo Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (70177244)
YASUNAGA Yuji Hiroshima University, Graduate School of Biomedical Sciences, Visiting professor, 大学院・医歯薬学総合研究科, 客員教授 (40253075)
SAKAI Akira Hiroshima University, Hospital, Assistant professor, 病院・講師 (70284221)
KUBO Tadahiko Hiroshima University, Graduate School of Biomedical Sciences, Assistant, 大学院・医歯薬学総合研究科, 助手 (70397959)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Bisphosphonate / Osteosarcoma / Chondrosarcoma / Ewing's sarcoma / 腫瘍細胞浸潤抑制 |
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| Research Abstract |
Little is known about the biological effects of bisphosphonates on primary malignant bone tumors. The purpose of this study was to investigate the antitumor effects of newly developed minodronate (MIN) on a variety of human malignant bone tumors. We examined the effects of MIN and clinically relevant incadronate (INC) on the proliferation, apoptosis, and cell cycle of two osteosarcoma (Saos-2,MG-63), two chondrosarcoma (SW1353,OUMS27), and two Ewing's sarcoma (RD-ES, SK-ES-1) cell lines. Furthermore, we investigated the anti-invasion effects of MIN on sarcoma cells and the effects of MIN on tumor growth in nude mice. MIN inhibited the viability of all six cell lines in a dose-dependent manner with IC_<50> values of 2.7-5.0 μM, which were significantly lower than those of INC. Importantly, both bisphosphonates affected the viability of normal bone marrow stromal cells much less than sarcoma cells. Both bisphosphonates induced cell cycle perturbation in all sarcoma cells tested and apoptosis in Saos-2 and SW1353 cells, although they failed to induce apoptosis in RD-ES and SK-ES-1 cells. MIN significantly suppressed invasion, even at a low concentration of 1 μM (p<0.01). Daily injection of 5 μg of MIN inhibited the growth of SK-ES-1 xenograft sarcoma in nude mice without loss of body weight. These findings suggest that MIN may have a beneficial adjuvant role in the treatment of patients with malignant bone tumors.
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