Acta Pharmacologica Sinica 2007 August; 28 (8): 1231-1235; doi: 10.1111/j.1745-7254.2007.00607.x

Acta Pharmacologica Sinica 2007 August; 28 (8): 1231-1235; doi: 10.1111/j.1745-7254.2007.00607.x

Original Article

Alendronate inhibits cell invasion and MMP-2 secretion in human chondrosarcoma cell line¹

Te-jen LAI^2,3, Sheng-feng HSU⁴, Te-mao LI⁴, Horng-chaung HSU⁵, Jaung-geng LIN⁴, Chin-jung HSU⁵, Ming-chih CHOU², Meng-chih LEE², Shun-fa YANG², Yi-chin FONG^5,6,7

²Institute of Medicine, Chung Shan Medical University, ³Department of Psychiatry, Chung Shan Medical University Hospital, Taiwan, China; ⁴Graduate Institute of Acupuncture Science, China Medical University, Taiwan, China; ⁵Department of Orthopaedic Surgery, China Medical University Hospital, Taiwan, China; ⁶School of Chinese Medicine, China Medical University, Taiwan, China

Aim: 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).

Methods: JJ012 cells were treated with alendronate of various concentrations up to 100 µmol/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.

Results: 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.

Conclusion: 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 chondro-sarcomas, as well as other malignant diseases.

Keywords: alendronate; bisphosphonate; chondrosarcoma; matrix metalloproteinase-2; invasion; migration

¹This study was supported by grants from China Medical University (No CMU-93-CM-15 and CMU-94-015) and China Medical University Hospital (No DMR-94-036 and DMR-95-067).

⁷Correspondence to Dr Yi-chin FONG.
Phn 88-64-2205-2121, ext 1903.
Fax 88-64-2245-2610.
E-mail yichin.fong@msa.hinet.net; s010002@csmu.edu.tw
Received 2007-01-01 Accepted 2007-02-13

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