[Protein tyrosine kinase inhibitor genistein suppresses in vitro invasion of HT1080 human fibrosarcoma cells].
OBJECTIVE
To investigate the effects of genistein on cancer invasion and associated cellular characteristics and explore the possibility of developing protein tyrosine kinase inhibitors as anti-metastasis drugs.


METHODS
HT1080 human fibrosarcoma cells were exposed to 20 mumol/L or 40 mumol/L genistein for 3 days. The abilities of the genistein-treated cells to invade through reconstituted matrigel or migrate through polycarbonate filters in transwell chambers were then investigated. Northern blot and laser densitometry were used to estimate the relative mRNA amounts of MMP-2, MMP-9 and TIMP-1 in the cells.


RESULTS
The ability of the genistein-treated HT1080 cells to invade the reconstituted basement membrane was decreased significantly (P < 0.01). In consistent with the lowered invasive potential, migration rates of the drug-treated cells decreased dramatically. genistein did not, however, significantly affect attachment of HT1080 cells on fibronectin, laminin or Matrigel. Though exposure to genistein led to a small increase in MMP-2 and MMP-9 gene expression, a much greater increase in the amount of TIMP-1 mRNA was observed. Imbalanced enhancement of gene expression between matrix metalloproteinases and their inhibitors in favor of the latter may imply that matrix degradation is impaired in the genistein-treated cells.


CONCLUSIONS
Genistein suppresses invasion of HT1080 cells at relatively low concentrations. genistein and other protein tyrosine kinase inhibitors might be valuable candidate drugs for the treatment of invasion and metastasis of cancer.
Yan
C
C
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050.
Han
R
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009361:Neoplasm Invasiveness; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019833:Genistein; D020780:Matrix Metalloproteinase 9