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论文题目: Targeting lung cancer stem-like cells with TRAIL gene armed oncolytic adenovirus
英文论文题目: Targeting lung cancer stem-like cells with TRAIL gene armed oncolytic adenovirus
第一作者: Yang, Y; Xu, HN; Huang, WD; Ding, M; Xiao, J; Yang, DM; Li, HG; Liu, XY; Chu, L
英文第一作者: Yang, Y; Xu, HN; Huang, WD; Ding, M; Xiao, J; Yang, DM; Li, HG; Liu, XY; Chu, L
联系作者: Chu, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Chu, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2015
卷: 19
期: 5
页码: 915-923
摘要: Lung cancer stem cell (LCSC) is critical in cancer initiation, progression, drug resistance and relapse. Disadvantages showed in conventional lung cancer therapy probably because of its existence. In this study, lung cancer cell line A549 cells propagated as spheroid bodies (named as A549 sphere cells) in growth factors-defined serum-free medium. A549 sphere cells displayed CSC properties, including chemo-resistance, increased proportion of G0/G1 cells, slower proliferation rate, ability of differentiation and enhanced tumour formation ability in vivo. Oncolytic adenovirus ZD55 carrying EGFP gene, ZD55-EGFP, infected A549 sphere cells and inhibited cell growth. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) armed oncolytic adenovirus, ZD55-TRAIL, exhibited enhanced cytotoxicity and induced A549 sphere cells apoptosis through mitochondrial pathway. Moreover, small molecules embelin, LY294002 and resveratrol improved the cytotoxicity of ZD55-TRAIL. In the A549 sphere cells xenograft models, ZD55-TRAIL significantly inhibited tumour growth and improved survival status of mice. These results suggested that gene armed oncolytic adenovirus is a potential approach for lung cancer therapy through targeting LCSCs.
英文摘要: Lung cancer stem cell (LCSC) is critical in cancer initiation, progression, drug resistance and relapse. Disadvantages showed in conventional lung cancer therapy probably because of its existence. In this study, lung cancer cell line A549 cells propagated as spheroid bodies (named as A549 sphere cells) in growth factors-defined serum-free medium. A549 sphere cells displayed CSC properties, including chemo-resistance, increased proportion of G0/G1 cells, slower proliferation rate, ability of differentiation and enhanced tumour formation ability in vivo. Oncolytic adenovirus ZD55 carrying EGFP gene, ZD55-EGFP, infected A549 sphere cells and inhibited cell growth. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) armed oncolytic adenovirus, ZD55-TRAIL, exhibited enhanced cytotoxicity and induced A549 sphere cells apoptosis through mitochondrial pathway. Moreover, small molecules embelin, LY294002 and resveratrol improved the cytotoxicity of ZD55-TRAIL. In the A549 sphere cells xenograft models, ZD55-TRAIL significantly inhibited tumour growth and improved survival status of mice. These results suggested that gene armed oncolytic adenovirus is a potential approach for lung cancer therapy through targeting LCSCs.
刊物名称: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
英文刊物名称: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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学科: Cell Biology; Research & Experimental Medicine
英文学科: Cell Biology; Research & Experimental Medicine
影响因子: 4.014
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论文类别: Article
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