Inhibitory effects of a new bisphosphonate, minodronate, on proliferation and invasion of a variety of malignant bone tumor cells
Journal of Orthopaedic Research Volume 24 Issue 6
Page 1138-1144
published_at 2006-05-16
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| File | |
| Title ( eng ) |
Inhibitory effects of a new bisphosphonate, minodronate, on proliferation and invasion of a variety of malignant bone tumor cells
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| Creator |
Shimose Shoji
Tanaka Kumi
Sakai Akira
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| Source Title |
Journal of Orthopaedic Research
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| Volume | 24 |
| Issue | 6 |
| Start Page | 1138 |
| End Page | 1144 |
| 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 IC50 values of 2.7 to 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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| Keywords |
bisphosphonate
osteosarcoma
chondrosarcoma
Ewing's sarcoma
antitumor effect
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| NDC |
Medical sciences [ 490 ]
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| Language |
eng
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| Resource Type | journal article |
| Publisher |
John Wiley & Sons Ltd.
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| Date of Issued | 2006-05-16 |
| Rights |
Copyright (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1138-1144, 2006
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| Publish Type | Author’s Original |
| Access Rights | open access |
| Source Identifier |
[ISSN] 0736-0266
[DOI] 10.1002/jor.20177
[NCID] AA10625350
[DOI] http://dx.doi.org/10.1002/jor.20177
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