title: Adenovirus-delivered wwox inhibited lung cancer growth in vivo in a mouse model.
abstract: Lung cancer is the most prevalent and deadly malignancy worldwide. This study investigated the possibility of inhibiting lung cancer in vivo with adenovirus-delivered WW domain-containing oxidoreductase (wwox). The lung cancer model was established by inoculating A549 lung cancer cells into the pleural space of nude mice. The control or wwox adenovirus was injected into the pleural space 7 days after cell inoculation and 14 days after first injection. The tumor number and burdens were measured 2 weeks after second virus injection. The carcinoembryonic antigen (CEA) and alpha-feto protein (AFP) levels in pleural effusion were analyzed by enzyme-linked immunosorbent assay. Apoptosis, proliferation and angiogenesis of tumor cells were assessed by terminal deoxinucleotidyl transferase-mediated dUTP-fluorescein nick end labeling assay, proliferating cell nuclear antigen (PCNA) and CD31 staining, respectively. Ectopic wwox significantly reduced both the number and size of lung tumors accompanied by substantially lower CEA and AFP levels in pleural effusion. The expression levels of Bcl2, Bcl-xL, vascular endothelial growth factor, PCNA-positive and CD31-positive cells in the tumors were significantly decreased, whereas levels of p21 and p73 and apoptotic cells markedly increased in mice receiving the wwox virus. These data demonstrated that wwox delivered by adenovirus was able to inhibit the growth of lung cancer in vivo, indicating the potential of using wwox as a gene therapy agent for lung cancer.
authors.affiliation: Department of Thoracic Surgery, The Affiliated Hospital of Jiangnan University and Wuxi Fourth People's Hospital, Wuxi, Jangsu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Thoracic Surgery, The Affiliated Hospital of Jiangnan University and Wuxi Fourth People's Hospital, Wuxi, Jangsu, China.
authors.forename: F
authors.initials: F
authors.lastname: Shou
authors.affiliation: Department of Thoracic Surgery, The Affiliated Hospital of Jiangnan University and Wuxi Fourth People's Hospital, Wuxi, Jangsu, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, The Affiliated Hospital of Jiangnan University and Wuxi Fourth People's Hospital, Wuxi, Jangsu, China.
authors.forename: Q
authors.initials: Q
authors.lastname: You
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics; D009389:Neovascularization, Pathologic; D010088:Oxidoreductases / Q000235:genetics*; D014161:Transduction, Genetic; D019076:Transgenes; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000074584:WW Domain-Containing Oxidoreductase; D023041:Xenograft Model Antitumor Assays
chemical_list: D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human