Plasmid Transfer of Plasminogen K1-5 Reduces Subcutaneous Hepatoma Growth by Affecting Inflammatory Factors

• Published in: BioMed research international 2014-01, Vol.2014 (2014), p.1-14
• Main Authors: Koch, Lea A., Schmitz, Volker, Strassburg, Christian P., Raskopf, Esther
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Proliferation; Cell Survival; Gene Transfer Techniques; Genetic Therapy; Hepatoma; Humans; Inflammation Mediators - metabolism; Laboratory animals; Liver cancer; Liver Neoplasms - pathology; Male; Mice; Microvessels - pathology; Phosphorylation; Plasmids - genetics; Plasmids - metabolism; Plasminogen - genetics; Plasminogen - therapeutic use; Recruitment; STAT3 Transcription Factor - metabolism; Subcutaneous Tissue - pathology; Thrombolytic drugs; Tumor Necrosis Factor-alpha - metabolism; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - secretion
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2014/656527

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.