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KMID : 0857020060210010358
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Kosin Medical Journal
2006 Volume.21 No. 1 p.358 ~ p.363
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Effects of zoledronic acid on expression of matrix metalloproteinase-2 and -14 and lung metastasis of osteosarcoma cell
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Kim Yong-Baek
Kwon Young-Ho
Kim Jae-Do
Kim Sang-Bum
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Abstract
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Purpose : Gelatinase A (MMP-2) and membrane-type metalloproteinase (MT1-MMP, MMP-14) play a critical role in metastasis. It was known that bisphosphonate acts not only to protect bone absorption but also to inhibit tumor invasion and metastasis. The aim of this study is to investigate the inhibition of MMP-2 and 14 in osteosarcoma by zoledronic acid, whether it can prevent lung metastasis in nude mouse.
Material and Method : Protein synthesis and mRNA expression of MMP-2 and MMP-14 cultured human MG-63 osteosarcoma and HOS osteosarcoma cell lines with zoledronic acids were measured. In vivo test, it was observed that the inhibitory effect of zoledronic acid on lung metastasis of osteosarcoma with nude mouse model.
Result : Zoledronic acid inhibited mRNA expression of MMP-14 and MMP-2 in cultured human MG-63 osteosarcoma and HOS osteosarcoma cell lines. Zoledronic acid decreased the intensity of activated 62KD MMP-2 in human MG-63 osteosarcoma and HOS osteosarcoma cell lines on gelatine zymography. Number of metastatic lung nodule decreased from 9.4 to 1.2 in MG-63 osteosarcoma cell line and from 8 to 1.6 in HOS osteosarcoma cell line with nude mouse model.
Conclusion : In vitro, zoledronic acid had an inhibitory effect on the MMP-14 and MMp-2, which also prevents lung metastasis of osteosarcoma in vivo. So, zoledronic acid could be used as one of good chemotherapeutic agents against metastasis of osteosarcoma.
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KEYWORD
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MMP-2, MMP-14, osteosarcoma, lung metastasis, zoledronate
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