Open AccessTargeting lung cancer stem‐like cells with TRAIL gene armed oncolytic adenovirus
Author(s) -
Yang Yu,
Xu Haineng,
Huang Weidan,
Ding Miao,
Xiao Jing,
Yang Dongmei,
Li Huaguang,
Liu XinYuan,
Chu Liang
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12397
Subject(s) - oncolytic virus , lung cancer , oncolytic adenovirus , cancer research , stem cell , cancer stem cell , gene , virology , biology , medicine , virus , oncology , genetics
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 ZD 55 carrying EGFP gene, ZD 55‐ EGFP , infected A549 sphere cells and inhibited cell growth. Tumour necrosis factor‐related apoptosis‐inducing ligand ( TRAIL ) armed oncolytic adenovirus, ZD 55‐ TRAIL , exhibited enhanced cytotoxicity and induced A549 sphere cells apoptosis through mitochondrial pathway. Moreover, small molecules embelin, LY 294002 and resveratrol improved the cytotoxicity of ZD 55‐ TRAIL . In the A549 sphere cells xenograft models, ZD 55‐ 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 LCSC s.