title: Gene therapy with biosynthetic nanoscale peptide Cecropin A driven by the survivin promoter for hepatocarcinoma cells.
abstract: The biosynthetic nanoscale peptide Cecropin A is postulated to disrupt microbial phospholipid membranes by forming stable or transient pores. We demonstrated previously that green fluorescent protein (GFP), driven by the survivin promoter, was expressed highly in HepG2 but not in LO2 cells when they were transfected with the recombinant plasmid reporter vector (pSURV-GFP). To investigate the selective killing effect of this survivin promoter-driven peptide toxin gene system on hepatocellular carcinoma (HCC) cells in vitro, the recombinant plasmid pSURV-Cecropin A was constructed. HepG2 and LO2 cells were then transfected with the recombinant plasmid, which was driven by the survivin promoter, and the effects of Cecropin A were evaluated. Forty-eight hours after transfection with pSURV-Cecropin A, the growth of HepG2 cells was inhibited significantly. This finding was confirmed further by immunoblotting, which revealed consistently suppressed expression of proliferating cell nuclear antigen (PCNA) and cysteinyl aspartate specific proteinase-3 (caspase-3). Data demonstrated that the plasmid carrying the gene for the Cecropin A fusion protein was constructed successfully, and that its specific expression in HepG2 cells could provide the basis for targeted gene therapy in HCC. The identification of novel gene therapies for cancer is highly desirable to reduce drug toxicity and improve therapeutic outcomes..
authors.forename: Lailing
authors.initials: L
authors.lastname: Gong
authors.forename: Lili
authors.initials: L
authors.lastname: Qu
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Li
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Li
authors.forename: Hongpan
authors.initials: H
authors.lastname: Xu
authors.forename: Peng
authors.initials: P
authors.lastname: Shen
authors.forename: Lu
authors.initials: L
authors.lastname: Pang
authors.forename: Rujun
authors.initials: R
authors.lastname: Gong
authors.forename: Guozhong
authors.initials: G
authors.lastname: Ji
authors.forename: Jin
authors.initials: J
authors.lastname: Si
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy* / Q000648:ultrastructure; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy / Q000648:ultrastructure; D010455:Peptides / Q000235:genetics / Q000627:therapeutic use*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000077022:Survivin
chemical_list: D023181:Antimicrobial Cationic Peptides; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D010455:Peptides; D000077022:Survivin; D049452:Green Fluorescent Proteins; C031161:cecropin A