Suppression of invasion of a hamster pancreatic cancer cell line by antisense oligonucleotides mutation-matched to K-ras gene.

The anti-invasive activity of antisense oligonucleotides (ASO) specific to the K-ras gene in hamster pancreatic cancer was investigated. HaP-T1, a cell culture derived from BHP-induced hamster pancreatic cancer, was used. After liposome-mediated transfection with mutation-matched and mutation-mismatched ASO in different concentrations, cell proliferation was studied by MTT and MTT-agarose methods. In vitro chemoinvasion assay with the reconstitution of a matrix of a basement membrane onto a filter in a Boyden chamber was performed. Mutation-matched ASO inhibited the tumor growth and invasiveness of HaP-T1 in a dose-dependent manner, while mutation-mismatched ASO were not effective in inhibiting invasion. The present study suggests that antisense oligonucleotides mutation-matched to the K-ras gene may be a new anticancer strategy for pancreatic cancer since they inhibited not only tumor growth but also invasiveness in vitro.