title: Tumor targeted gene therapy with plasmid expressing human tumor necrosis factor alpha in vitro and in vivo.
abstract: We have assessed the effect of exogenous human tumor necrosis factor alpha (hTNFalpha) in three human cancer cell lines; MDA-MB-361 (breast adenocarcinoma), HCT 116 (colon carcinoma) and 8-MG-BA (glioma). In vitro transfection of a plasmid containing hTNFalpha under the control of a hybrid promoter resulted in expression of hTNFalpha gene in all three cell lines and secretion into the culture medium was seen with MDA-MB-361 cells. Flow cytometric analysis showed a significant increase in apoptotic and necrotic cells in MDA-MB-361 and to a lesser extent in HCT 116 cells. Increased apoptosis was confirmed by an increase in pro-caspase 3 activation. No effects of hTNFalpha expression were seen in 8-MG-BA cells. Intratumoral delivery of the hTNFalpha expression plasmid into MDA-MB-361 tumor xenografts grown in nude mice caused hemorrhagic tumor necrosis. This strategy may be a simple and promising gene therapy approach to the treatment of some human tumors.
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovak Republic. exonada@savba.sk
authors.forename: A
authors.initials: A
authors.lastname: Pastorakova
authors.forename: K
authors.initials: K
authors.lastname: Hlubinova
authors.forename: J
authors.initials: J
authors.lastname: Bodo
authors.forename: J
authors.initials: J
authors.lastname: Libby
authors.forename: B
authors.initials: B
authors.lastname: Rychly
authors.forename: G
authors.initials: G
authors.lastname: Margison
authors.forename: C
authors.initials: C
authors.lastname: Altaner
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009336:Necrosis; D010957:Plasmids; D011401:Promoter Regions, Genetic; D019076:Transgenes; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha