The targeted inhibitory effects of human amniotic fluid stem cells carrying CXCR4 promoter and DAL-1 on non-small cell lung carcinoma growth.
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.
Center for Respiratory Pathology, State Key Lab of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
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Li
Department of Pathology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, People's Republic of China.
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Li
Department of Pathology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, People's Republic of China.
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Cai
Department of Pathology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, People's Republic of China.
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Wang
Department of Pathology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, People's Republic of China.
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Xie
Department of Pathology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, People's Republic of China.
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Liu
Department of Pathology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, People's Republic of China.
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Zhang
D000256:Adenoviridae / Q000235:genetics; D000653:Amniotic Fluid / Q000166:cytology; D000818:Animals; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics* / Q000627:therapeutic use; D011401:Promoter Regions, Genetic; D019718:Receptors, CXCR4 / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000627:therapeutic use; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
C116887:EPB41L3 protein, human; D008840:Microfilament Proteins; D019718:Receptors, CXCR4; D025521:Tumor Suppressor Proteins