Lai Te-jen, Hsu Sheng-feng, Li Te-mao, Hsu Horng-chaung, Lin Jaung-geng, Hsu Chin-jung, Chou Ming-chih, Lee Meng-chih, Yang Shun-fa, Fong Yi-chin
Institute of Medicine, Chung Shan Medical University, Department of Psychiatry, Chung Shan Medical University Hospital, Taiwan, China.
Acta Pharmacol Sin. 2007 Aug;28(8):1231-5. doi: 10.1111/j.1745-7254.2007.00607.x.
Chondrosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. The aim of the present study was to investigate the effect of alendronate, a bisphosphonate, on the invasion and migration of human chondrosarcoma cells (JJ012).
JJ012 cells were treated with alendronate of various concentrations up to 100 micromol/L for a specified period, and then gelatin zymography and matrigel invasion assay was performed to study the effects of alendronate on matrix metalloproteinase (MMP)-2 activity and the invasion ability of JJ012 cells, respectively.
Our data showed that alendronate exerted a dose- and time-dependent inhibitory effect on the invasion and migration of JJ012 cells. Furthermore, gelatin zymography and RT-PCR showed that alendronate treatment decreased the activity and mRNA levels of MMP-2 in a concentration-dependent manner.
Our findings suggest that alendronate may reduce MMP-2 secretion at the transcriptional and translational levels, and inhibit the invasion of chondrosarcoma cell. Therefore, alendronate may be a potential candidate for the systemic therapy of chondrosarcomas, as well as other malignant diseases.
软骨肉瘤是一种原发性恶性骨肿瘤，对化疗和放疗反应均较差。本研究旨在探讨双膦酸盐阿仑膦酸钠对人软骨肉瘤细胞（JJ012）侵袭和迁移的影响。
用浓度高达100微摩尔/升的不同浓度阿仑膦酸钠处理JJ012细胞一段特定时间，然后分别进行明胶酶谱分析和基质胶侵袭试验，以研究阿仑膦酸钠对基质金属蛋白酶（MMP）-2活性及JJ012细胞侵袭能力的影响。
我们的数据表明，阿仑膦酸钠对JJ012细胞的侵袭和迁移具有剂量和时间依赖性抑制作用。此外，明胶酶谱分析和逆转录-聚合酶链反应显示，阿仑膦酸钠处理以浓度依赖性方式降低了MMP-2的活性和mRNA水平。
我们的研究结果表明，阿仑膦酸钠可能在转录和翻译水平降低MMP-2的分泌，并抑制软骨肉瘤细胞的侵袭。因此，阿仑膦酸钠可能是软骨肉瘤以及其他恶性疾病全身治疗的潜在候选药物。
