title: VSV-MP gene therapy strategy inhibits tumor growth in nude mice model of human lung adenocarcinoma.
abstract: Vesicular stomatitis virus (VSV) matrix protein (MP) can induce in vitro apoptosis of tumor cells in the absence of other viral components. Here, the antitumor activity of VSV-MP against lung adenocarcinoma was investigated in vivo. A pVAX-plasmid DNA encoding VSV-MP and control empty vectors (pVAX) were constructed and wrapped-up with liposome. A549 and Spc-A1 human lung adenocarcinoma cells were transfected with liposomal-VSV-MP (Lip-MP) or Lip-pVAX and then examined for cell viability or apoptosis using Hoechst/propidium iodide staining by flow cytometry, and further demonstrated by caspase/poly ADP-ribose polymerase (PARP) cleavage analysis. For the in vivo study, A549 and Spc-A1 lung carcinoma models in nude mice were established and randomly assigned into three groups to receive eight 2-weekly intravenous administrations of medium alone as control, Lip-pVAX or Lip-MP, respectively. Subsequently, Lip-MP significantly reduced tumor growth and prolonged the survival of tumor-bearing mice compared with Lip-pVAX and control agents (P<0.05), with much higher apoptosis index of both in vivo and in vitro tumor cells, respectively (P<0.05). In addition, in vivo antitumoral effect was associated with natural killer-(NK) cell congregation without evidence of toxicity. These observations suggest that systemically delivering Lip-MP has a specific dual antitumor activity in human lung adenocarcinoma by inducing apoptosis and possibly stimulating NK-cell responses, it may provide a clue for developing new therapeutic approaches against human lung adenocarcinoma.
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors: X-M
authors: XM
authors: Jing
authors: Y-J
authors: YJ
authors: Wen
authors: W
authors: W
authors: Shi
authors: Q-Q
authors: QQ
authors: Tang
authors: J
authors: J
authors: Li
authors: X-C
authors: XC
authors: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008081:Liposomes; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; C094460:M protein, Vesicular stomatitis virus; D014763:Viral Matrix Proteins