title: Salmonella typhimurium mediated delivery of Apoptin in human laryngeal cancer.
abstract: An effective cancer therapeutic should target tumours specifically with limited systemic toxicity. Here, we transformed an attenuated Salmonella typhimurium (S. typhimurium) with an Apoptin expressing plasmid into a human laryngeal carcinoma cell line. The expression of the inserted gene was measured using fluorescence and immunoblotting assays. The attenuated S. typhimurium-mediated Apoptin significantly decreased cytotoxicity and strongly increased cell apoptosis through the activation of caspase-3. The process was mediated by Bax, cytochrome c and caspase-9. A syngeneic nude murine tumour model was used to determine the anti-tumour effects of the recombinant bacteria in vivo. Systemic injection of the recombinant bacteria with and without re-dosing caused significant tumour growth delay and reduced tumour microvessel density, thereby extending host survival. Our findings indicated that the use of recombinant Salmonella typhimurium as an Apoptin expression vector has potential cancer therapeutic benefits.
authors.affiliation: 1. Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
authors.forename: Guo-fang
authors.initials: GF
authors.lastname: Guan
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Li-ming
authors.initials: LM
authors.lastname: Liu
authors.forename: Chun-shun
authors.initials: CS
authors.lastname: Jin
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: De-jun
authors.initials: DJ
authors.lastname: Zhang
authors.forename: Duo-jiao
authors.initials: DJ
authors.lastname: Yu
authors.forename: Hong-wei
authors.initials: HW
authors.lastname: Cao
authors.forename: Yan-qing
authors.initials: YQ
authors.lastname: Lu
authors.forename: Lian-ji
authors.initials: LJ
authors.lastname: Wen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D036022:Capsid Proteins / Q000008:administration & dosage / Q000235:genetics*; D053148:Caspase 3 / Q000096:biosynthesis; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D012486:Salmonella typhimurium / Q000737:chemistry / Q000235:genetics*
chemical_list: D036022:Capsid Proteins; C091717:VP3 protein, Chicken anemia virus; D053148:Caspase 3; D053453:Caspase 9
keywords: Apoptin; apoptosis; attenuated Salmonella typhimurium; laryngeal cancer; tumours specifically therapy