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

Acta Pharmacol Sin. 2007 Aug;28(8):1231-5. doi: 10.1111/j.1745-7254.2007.00607.x.

Abstract

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 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.

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 chondrosarcomas, as well as other malignant diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate / pharmacology*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / enzymology
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival / drug effects
  • Chondrosarcoma / drug therapy*
  • Chondrosarcoma / enzymology
  • Chondrosarcoma / pathology
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Neoplasm Invasiveness

Substances

  • Matrix Metalloproteinase 2
  • Alendronate