Antisense oligonucleotides specific to mutated K-ras genes inhibit invasiveness of human pancreatic cancer cell lines

Pancreatology. 2001;1(4):314-9. doi: 10.1159/000055830.

Abstract

Background/aims: Point mutations of the K-ras gene are detected in > 90% of human pancreatic cancers and may play an important role in tumorigenesis. However, correlations between mutant K-ras and the invasive activity of the tumor have remained unclarified.

Methods: 17-merphosphorothioate antisense oligonucleotides targeting K-ras point mutations were transfected into three kinds of human pancreatic cancer cell lines (MIAPaCa-2, PANC-1, and BxPC-3), and the invasive activity was investigated using an in vitro chemoinvasion assay.

Results: Antisense oligonucleotides strongly inhibited the invasive activity of the cell lines with mutant K-ras genes (MIAPaCa-2, PANC-1), but not in that with a wild-type K-ras (BxPC-3).

Conclusion: Antisense oligonucleotides specific to mutated K-ras genes inhibited the invasiveness of human pancreatic cancer cell lines. Specific antisense therapy to the point mutation of K-ras might be a new anticancer strategy for pancreatic cancer.

MeSH terms

  • Blotting, Western
  • Cell Line
  • Coloring Agents
  • DNA, Neoplasm / genetics
  • Genes, ras / genetics*
  • Humans
  • Mutation / genetics
  • Neoplasm Invasiveness / pathology*
  • Oligonucleotides, Antisense / pharmacology*
  • Pancreatic Neoplasms / pathology*
  • Tetrazolium Salts
  • Thiazoles
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Coloring Agents
  • DNA, Neoplasm
  • Oligonucleotides, Antisense
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue