Introduction of a survivin gene-specific small inhibitory RNA inhibits growth of pancreatic cancer cells

Anticancer Res. 2005 Nov-Dec;25(6B):3967-72.

Abstract

Background: The anti-apoptotic molecule survivin is expressed in human cancers of various origins. Since this molecule possesses multiple functions, including apoptosis inhibition, cell cycle promotion and enhancement of Fas ligand expression, survivin has attracted growing attention as a target in cancer treatment. A survivin-specific small inhibitory RNA (siRNA) was introduced into pancreatic cancer cells to investigate its effect on cancer cell growth.

Materials and methods: Survivin mRNA and protein expression were examined by RT-PCR and Western blotting, respectively. DNA histogram analysis was performed using a flow cytometer.

Results: The introduction of survivin-specific siRNA reduced survivin mRNA and protein expression in PANC-1 cells by over 90% and to an undetected amount, respectively, and induced growth inhibition. The siRNA transfectants showed pronounced morphological changes including enlargement of cells and multinucleation. siRNA transfectants did not show cell cycle arrest, but underwent apoptosis.

Conclusion: Our data suggest that the use of survivin-specific siRNA deserves further investigation as a novel approach to cancer therapy.

MeSH terms

  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Genetic Therapy / methods
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / genetics*
  • Neoplasm Proteins / genetics*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / therapy
  • RNA Interference
  • RNA, Small Interfering / genetics*
  • Survivin
  • Transfection

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Survivin