The targeted inhibitory effects of human amniotic fluid stem cells carrying CXCR4 promoter and DAL-1 on non-small cell lung carcinoma growth

被引:8
作者
Li, L. [1 ]
Li, S. [2 ]
Cai, T. [2 ]
Wang, H. [2 ]
Xie, X. [2 ]
Liu, Z. [2 ]
Zhang, Y. [2 ]
机构
[1] Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Ctr Resp Pathol, Guangzhou, Guangdong, Peoples R China
[2] Guangzhou Med Univ, Sch Basic Med Sci, Dept Pathol, Guangzhou, Guangdong, Peoples R China
关键词
CONDITIONALLY-REPLICATIVE ADENOVIRUS; PROTEIN; 4.1B; CANCER; DELIVERY; GENE;
D O I
10.1038/gt.2015.90
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The differentially expressed in adenocarcinoma of the lung-1 (DAL-1) protein has been demonstrated to be suppressive to various types of tumors including lung cancer. This study aimed to determine the targeted effects of human amniotic fluid stem cells (hAFS cells) carrying CXCR4 promoter driven conditionally replicable adenovirus vector overexpressing DAL-1 (Ad-CXCR4-DAL-1) on non-small cell lung carcinoma (NSCLC) growth. The apoptotic effects of virus vectors were assessed using flow cytometry, and the cytotoxicity analyzed by CCK-8 assay. In vivo imaging system was used to determine the homing capability of hAFS cells. A549 cell xenograft mouse model was created to assess the in vivo effect of DAL-1 overexpression on NSCLC growth. We found that infection of Ad-CXCR4-DAL-1 increased the apoptosis of A549 NSCLC cells but not 16HBE normal human bronchial epithelial cells. Ad-CXCR4-DAL-1 administered via intratumoral injection led to significant reduced growth and greater necrosis of A549 xenograft tumors comparing to null vector treated animals. When infused via tail vein, hAFS cells carrying Ad-CXCR4-DAL-1 homed to lung cancer xenografts, caused virus replication and DAL-1 overexpression, and led to significant lower growth and greater necrosis of A549 cell xenografts comparing to non-treatment control. In conclusion, hAFS cells are capable of carrying Ad-CXCR4-DAL-1 vectors, specifically targeting to lung cancer, and causing oncolytic effects when administered in vivo.
引用
收藏
页码:214 / 222
页数:9
相关论文
共 29 条
[1]   Generation of a novel, cyclooxygenase-2-targeted, interferon-expressing, conditionally replicative adenovirus for pancreatic cancer therapy [J].
Armstrong, Leonard ;
Arrington, Amanda ;
Han, Joohee ;
Gavrikova, Tatyana ;
Brown, Eric ;
Yamamoto, Masato ;
Vickers, Selwyn M. ;
Davydova, Julia .
AMERICAN JOURNAL OF SURGERY, 2012, 204 (05) :741-750
[2]   Fetal Mesenchymal Stem Cells in Cancer Therapy [J].
Bitsika, Vasiliki ;
Vlahou, Antonia ;
Roubelakis, Maria G. .
CURRENT STEM CELL RESEARCH & THERAPY, 2013, 8 (02) :133-143
[3]   Third trimester NG2-positive amniotic fluid cells are effective in improving repair in spinal cord injury [J].
Bottai, Daniele ;
Scesa, Giuseppe ;
Cigognini, Daniela ;
Adami, Raffaella ;
Nicora, Emanuela ;
Abrignani, Sergio ;
Di Giulio, Anna Maria ;
Gorio, Alfredo .
EXPERIMENTAL NEUROLOGY, 2014, 254 :121-133
[4]   Evidence for protein 4.1B acting as a metastasis suppressor [J].
Cavanna, Tamara ;
Pokorna, Eva ;
Vesely, Pavel ;
Gray, Colin ;
Zicha, Daniel .
JOURNAL OF CELL SCIENCE, 2007, 120 (04) :606-616
[5]   Oncolytic viruses [J].
Chiocca, EA .
NATURE REVIEWS CANCER, 2002, 2 (12) :938-950
[6]   The Changing Epidemic of Lung Cancer and Occupational and Environmental Risk Factors [J].
Dresler, Carolyn .
THORACIC SURGERY CLINICS, 2013, 23 (02) :113-+
[7]   RETRACTED: The prognosis and clinicopathology of CXCR4 in gastric cancer patients: a meta-analysis (Retracted article. See April, 2017) [J].
Han, Mingzhi ;
Lv, Shunzeng ;
Zhang, Ya ;
Yi, Ruiyang ;
Huang, Bin ;
Fu, Hanhui ;
Bian, Ruixiang ;
Li, Xingang .
TUMOR BIOLOGY, 2014, 35 (05) :4589-4597
[8]   Replication-selective adenoviruses as oncolytic agents [J].
Heise, C ;
Kirn, DH .
JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (07) :847-851
[9]   Vitamin D3-Inducible Mesenchymal Stem Cell-Based Delivery of Conditionally Replicating Adenoviruses Effectively Targets Renal Cell Carcinoma and Inhibits Tumor Growth [J].
Hsiao, Wan-Chi ;
Sung, Shian-Ying ;
Liao, Chia-Hui ;
Wu, Hsi-Chin ;
Hsieh, Chia-Ling .
MOLECULAR PHARMACEUTICS, 2012, 9 (05) :1396-1408
[10]   The potential of mesenchymal stem cells derived from amniotic membrane and amniotic fluid for neuronal regenerative therapy [J].
Kim, Eun Young ;
Lee, Kyung-Bon ;
Kim, Min Kyu .
BMB REPORTS, 2014, 47 (03) :135-140