Targeting lung cancer stem‐like cells with TRAIL gene armed oncolytic adenovirus

Journal of Cellular and Molecular Medicine

Yu Yang³  Haineng Xu³  Weidan Huang³  Miao Ding³  Jing Xiao²  Dongmei Yang¹  Huaguang Li³  Xin-Yuan Liu³ 

[1] Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci-Tech University, Hangzhou, China;College of Life Science, Henan Normal University, Xinxiang, Henan, China;State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

关键词: lung cancer stem‐like cells;    A549 sphere cells;    oncolytic adenovirus;    ZD55‐TRAIL;    apoptosis;   

DOI  :  10.1111/jcmm.12397

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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