A combination of a DNA-chimera siRNA against PLK-1 and zoledronic acid suppresses the growth of malignant mesothelioma cells in vitro

Cancer Lett. 2010 Aug 28;294(2):245-53. doi: 10.1016/j.canlet.2010.02.008. Epub 2010 Mar 4.

Abstract

Although novel agents effective against malignant mesothelioma (MM) have been developed, the prognosis of patients with MM is still poor. We generated a DNA-chimeric siRNA against polo-like kinase-1 (PLK-1), which was more stable in human serum than the non-chimeric siRNA. The chimeric PLK-1 siRNA inhibited MM cell proliferation through the induction of apoptosis. Next, we investigated the effects of zoledronic acid (ZOL) on MM cells, and found that ZOL also induced apoptosis in MM cells. Furthermore, ZOL augmented the inhibitory effects of the PLK-1 siRNA. In conclusion, combining a PLK-1 siRNA with ZOL treatment is an attractive strategy against MM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / genetics*
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Chimera / genetics
  • Combined Modality Therapy
  • DNA / blood
  • DNA / genetics*
  • Diphosphonates / pharmacology*
  • Genetic Therapy / methods
  • Humans
  • Imidazoles / pharmacology*
  • Mesothelioma / enzymology
  • Mesothelioma / genetics
  • Mesothelioma / pathology
  • Mesothelioma / therapy*
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / genetics*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics*
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / blood
  • RNA, Small Interfering / genetics
  • Transfection
  • Zoledronic Acid

Substances

  • Cell Cycle Proteins
  • Diphosphonates
  • Imidazoles
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Zoledronic Acid
  • DNA
  • Protein Serine-Threonine Kinases