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


CONCLUSIONS
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.
Lai
Te-jen
TJ
Institute of Medicine, Chung Shan Medical University, Department of Psychiatry, Chung Shan Medical University Hospital, Taiwan, China.
Hsu
Sheng-feng
SF
Li
Te-mao
TM
Hsu
Horng-chaung
HC
Lin
Jaung-geng
JG
Hsu
Chin-jung
CJ
Chou
Ming-chih
MC
Lee
Meng-chih
MC
Yang
Shun-fa
SF
Fong
Yi-chin
YC
D019386:Alendronate / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival / Q000187:drug effects; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness
D020778:Matrix Metalloproteinase 2; D019386:Alendronate