title: Targeting lung cancer stem-like cells with TRAIL gene armed oncolytic adenovirus.
abstract: 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.
authors: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Yu
authors: Y
authors: Yang
authors: Haineng
authors: H
authors: Xu
authors: Weidan
authors: W
authors: Huang
authors: Miao
authors: M
authors: Ding
authors: Jing
authors: J
authors: Xiao
authors: Dongmei
authors: D
authors: Yang
authors: Huaguang
authors: H
authors: Li
authors: Xin-Yuan
authors: XY
authors: Liu
authors: Liang
authors: L
authors: Chu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D016227:Benzoquinones / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy / Q000821:virology; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009025:Morpholines / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D016227:Benzoquinones; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D013267:Stilbenes; D053221:TNF-Related Apoptosis-Inducing Ligand; D049452:Green Fluorescent Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000077185:Resveratrol; C010945:embelin
keywords: A549 sphere cells; ZD55-TRAIL; apoptosis; lung cancer stem-like cells; oncolytic adenovirus