Transfection of antisense oligodeoxynucleotide inhibits heparanase gene expression and invasive ability of human pancreatic cancer cellin vitro

Abstract

Extracellular matrix (ECM) degradation is an essential step that allows tumor cells to penetrate a tissue barrier and become metastatic. Heparanase (HPSE) is an endoglycosidase that specifically degrades heparin sulfate proteoglycans (HSPG), a chief component of ECM, HPSE is not expressed in normal epithelial cells but can be detected in a variety of human carcinomas including pancreatic cancer. In the present study, human pancreatic cancer cell line Panc-1 was transfected with HPSE antisense oligodeoxynucleotide (AS-ODN)in vitro, then the inhibitory effect of AS-ODN on HPSE gene expression and invasive ability of Panc-1 cellsin vitro was examined. The HPSE mRNA and protein expression of Panc-1 cells transfected with AS-ODN was significantly inhibited. However, there were no marked inhibitory effects in Panc-1 cells treated with nonsense oligodeoxynucleotide (NS-ODN). Moreover, a modified Boyden chamber assay demonstrated that transfection with HPSE AS-ODN significantly inhibited invasive potential of Panc-1 cellsin vitro after AS-ODN transfection. This suggests that HPSE AS-ODN may contribute to the inhibition of HPSE mRNA and protein expression, and results in a decrease of the invasive ability of Panc-1in vitro.

Keywords

heparanase / antisense oligodeoxynucleotide / invasion / pancreatic cancer