Antisense Deoxyoligonucleotides Inhibit Activities of Matrix Metalloproteinase-2 in Human Fibrosarcoma HT1080 Cells.
- Author:
Jung Sun PARK
1
;
Dong On YANG
;
Seon Hee LIM
;
Hyeon Gyeong YOO
;
Heyon Na CHO
;
Young Do JUNG
;
Sae Jong KIM
;
Sun Sik CHUNG
;
Boo Ahn SHIN
Author Information
1. Research Institute of Medical Sciences, Chonnam National University, Gwangju, Korea. bashin@chonnam.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Matrix metalloproteinases-2;
Antisense oligodeoxynucleotides;
Tumor invasion;
Metastasis
- MeSH:
Basement Membrane;
Blotting, Northern;
Blotting, Western;
Collagenases;
Fibrosarcoma*;
Gelatin;
Humans*;
Matrix Metalloproteinase 2*;
Neoplasm Metastasis;
Oligodeoxyribonucleotides;
RNA, Messenger
- From:Cancer Research and Treatment
2002;34(6):444-449
- CountryRepublic of Korea
- Language:English
-
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.
