Plasmid transfer of plasminogen K1-5 reduces subcutaneous hepatoma growth by affecting inflammatory factors

Biomed Res Int. 2014:2014:656527. doi: 10.1155/2014/656527. Epub 2014 May 8.

Abstract

There is evidence that plasminogen K1-5 (PlgK1-5) directly affects tumour cells and inflammation. Therefore, we analysed if PlgK1-5 has immediate effects on hepatoma cells and inflammatory factors in vitro and in vivo. In vitro, effects of plasmid encoding PlgK1-5 (pK1-5) on Hepa129, Hepa1-6, and HuH7 cell viability, apoptosis, and proliferation as well as VEGF and TNF-alpha expression and STAT3-phosphorylation were investigated. In vivo, tumour growth, proliferation, vessel density, and effects on vascular endothelial growth factor (VEGF) and tumour necrosis factor alpha (TNF-alpha) expression were examined following treatment with pK1-5. In vivo, pK1-5 halved cell viability; cell death was increased by up to 15% compared to the corresponding controls. Proliferation was not affected. VEGF, TNF-alpha, and STAT3-phosphorylation were affected following treatment with pK1-5. In vivo, ten days after treatment initiation, pK1-5 reduced subcutaneous tumour growth by 32% and mitosis by up to 77% compared to the controls. Vessel density was reduced by 50%. TNF-alpha levels in tumour and liver tissue were increased, whereas VEGF levels in tumours and livers were reduced after pK1-5 treatment. Taken together, plasmid gene transfer of PlgK1-5 inhibits hepatoma (cell) growth not only by reducing vessel density but also by inducing apoptosis, inhibiting proliferation, and triggering inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Gene Transfer Techniques*
  • Genetic Therapy
  • Humans
  • Inflammation Mediators / metabolism*
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Microvessels / pathology
  • Phosphorylation
  • Plasmids / genetics
  • Plasmids / metabolism*
  • Plasminogen / genetics*
  • Plasminogen / therapeutic use*
  • STAT3 Transcription Factor / metabolism
  • Subcutaneous Tissue / pathology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Inflammation Mediators
  • STAT3 Transcription Factor
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Plasminogen