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VSV-MP gene therapy strategy inhibits tumor growth in nude mice model of human lung adenocarcinoma

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机构: [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People’s Republic of China [2]Department of Chemotherapy, Sichuan Cancer Hospital, Chengdu, Sichuan, People’s Republic of China
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关键词: vesicular stomatitis virus matrix protein apoptosis lung adenocarcinoma cationic liposome NK-cell accumulation

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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. Cancer Gene Therapy (2012) 19, 101-109; doi: 10.1038/cgt.2011.71; published online 4 November 2011

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出版当年[2012]版:
大类 | 3 区 医学
小类 | 3 区 生物工程与应用微生物 3 区 遗传学 3 区 医学:研究与实验 3 区 肿瘤学
最新[2023]版:
大类 | 3 区 医学
小类 | 2 区 生物工程与应用微生物 3 区 遗传学 3 区 医学:研究与实验 4 区 肿瘤学
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出版当年[2012]版:
Q2 ONCOLOGY Q2 GENETICS & HEREDITY Q2 MEDICINE, RESEARCH & EXPERIMENTAL Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
最新[2023]版:
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 ONCOLOGY

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第一作者机构: [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People’s Republic of China [2]Department of Chemotherapy, Sichuan Cancer Hospital, Chengdu, Sichuan, People’s Republic of China
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通讯机构: [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People’s Republic of China [*1]West China Medical School, Sichuan University, Keyuan Road 4, Chengdu, Sichuan 610041, People’s Republic of China
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