Cancer Res Treat.  2002 Dec;34(6):444-449.

Antisense Deoxyoligonucleotides Inhibit Activities of Matrix Metalloproteinase-2 in Human Fibrosarcoma HT1080 Cells

• Park JS
• Yang DO
• Lim SH
• Yoo HG
• Cho HN
• Jung YD
• Kim SJ
• Chung SS
• Shin BA

Abstract

PURPOSE: MMP-2, 72 kDa-type IV collagenase, plays a major role in the migration and growth of tumor cells, a process that requires the disintegration of basement membrane. Activation of MMP-2 is correlated with the invasiveness of various tumors. The aim of this study was to determine the sequence-specific phosphorothioated oligodeoxynucleotides (ODNs) inhibiting the translation of MMP-2 mRNA and the subsequent invasiveness of tumor cells.
MATERIALS AND METHODS
Eight types of antisense ODNs were designed and each (8micro gram/ml) were transfected into HT1080 cells. The effects of these antisense ODNs on MMP expression were examined by gelatin zymography, Western blot, Northern blot and matrigel assay.
RESULTS
Antisense-5 (+904~923), antisense-6 (+1274~+1293) and antisense-7 (+1646~+1665) reduced the MMP-2 activity of the culture supernatant in HT1080 fibrosarcoma cells. Treatment with antisense-6 showed inhibition of MMP-2 mRNA and protein, and in vitro invasion in a dose-dependent manner.
CONCLUSION
Antisense-6 might be one of the therapeutic candidates for tumor invasion and metastasis.

Keyword

Matrix metalloproteinases-2; Antisense oligodeoxynucleotides; Tumor invasion; Metastasis

MeSH Terms

Basement Membrane
Blotting, Northern
Blotting, Western
Collagenases
Fibrosarcoma*
Gelatin
Humans*
Matrix Metalloproteinase 2*
Neoplasm Metastasis
Oligodeoxyribonucleotides
RNA, Messenger
Collagenases
Gelatin
Matrix Metalloproteinase 2
Oligodeoxyribonucleotides
RNA, Messenger