title: Plasmid transfer of plasminogen K1-5 reduces subcutaneous hepatoma growth by affecting inflammatory factors.
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.
authors.affiliation: Department of Inner Medicine I, University of Hospital Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Lea A
authors.initials: LA
authors.lastname: Koch
authors.affiliation: Krankenhaus Marienwörth, Mühlenstrasse 39, 55543, Bad Kreuznach, Germany.
authors.forename: Volker
authors.identifier: 0000-0002-0819-7624
authors.initials: V
authors.lastname: Schmitz
authors.affiliation: Department of Inner Medicine I, University of Hospital Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Strassburg
authors.affiliation: Department of Inner Medicine I, University of Hospital Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Esther
authors.initials: E
authors.lastname: Raskopf
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D055806:Microvessels / Q000473:pathology; D010766:Phosphorylation; D010957:Plasmids / Q000235:genetics / Q000378:metabolism*; D010958:Plasminogen / Q000235:genetics* / Q000627:therapeutic use*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D010958:Plasminogen