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Alendronate inhibits cell invasion and MMP-2 secretion in human chondrosarcoma cell line
Te-jen Lai1, Sheng-feng Hsu, Te-mao Li
1Institute of Medicine, Chung Shan Medical University, Department of Psychiatry, Chung Shan Medical University Hospital, 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 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.
Insights
Alendronate, a bisphosphonate, inhibits chondrosarcoma cell invasion and migration by reducing matrix metalloproteinase-2 (MMP-2) activity. This suggests alendronate
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Chondrosarcoma is a primary bone tumor with poor response to conventional therapies.
- Chemotherapy and radiation therapy are often ineffective against chondrosarcoma.
Purpose of the Study:
- To investigate the anti-invasive and anti-migratory effects of alendronate on human chondrosarcoma cells (JJ012).
- To determine the impact of alendronate on matrix metalloproteinase-2 (MMP-2) in chondrosarcoma.
Main Methods:
- JJ012 cells were treated with varying concentrations of alendronate.
- Gelatin zymography and matrigel invasion assays were used to assess MMP-2 activity and cell invasion.
- Reverse transcription polymerase chain reaction (RT-PCR) was employed to analyze MMP-2 mRNA levels.
Main Results:
- Alendronate demonstrated a dose- and time-dependent inhibition of chondrosarcoma cell invasion and migration.
- Alendronate significantly decreased MMP-2 activity and mRNA expression in a concentration-dependent manner.
- The drug reduced MMP-2 secretion at both transcriptional and translational levels.
Conclusions:
- Alendronate effectively inhibits chondrosarcoma cell invasion and migration.
- The mechanism involves the downregulation of MMP-2 at the transcriptional and translational levels.
- Alendronate shows potential as a therapeutic agent for chondrosarcoma and other malignancies.
