Protein tyrosine kinase inhibitor genistein suppresses in vitro invasion of HT1080 human fibrosarcoma cells

Chunhong Yan, R. Han

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 μmol/L or 40 μmol/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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)171-174
Number of pages4
JournalChinese Journal of Oncology
Volume21
Issue number3
StatePublished - Jul 3 1999
Externally publishedYes

Fingerprint

Genistein
Fibrosarcoma
Protein Kinase Inhibitors
Protein-Tyrosine Kinases
Matrix Metalloproteinases
polycarbonate
Tissue Inhibitor of Metalloproteinase-1
Pharmaceutical Preparations
Neoplasm Metastasis
Gene Expression
In Vitro Techniques
Messenger RNA
Matrix Metalloproteinase Inhibitors
Densitometry
Laminin
Fibronectins
Basement Membrane
Northern Blotting
Neoplasms
Lasers

Keywords

  • Fibrosarcoma
  • Genistein
  • Neoplasm invasion
  • Protein tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Protein tyrosine kinase inhibitor genistein suppresses in vitro invasion of HT1080 human fibrosarcoma cells. / Yan, Chunhong; Han, R.

In: Chinese Journal of Oncology, Vol. 21, No. 3, 03.07.1999, p. 171-174.

Research output: Contribution to journalArticle

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abstract = "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 μmol/L or 40 μmol/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. Conclusion 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.",
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N2 - 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 μmol/L or 40 μmol/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. Conclusion 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.

AB - 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 μmol/L or 40 μmol/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. Conclusion 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.

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