title: Adenovirus-mediated ING4/PTEN double tumor suppressor gene co-transfer modified by RGD enhances antitumor activity in human nasopharyngeal carcinoma cells.
abstract: Inhibitor of growth-4 (ING4) is a member of the inhibitor of growth (ING) family and acts as a tumor suppressor protein. PTEN is a phosphatase and shows potent and extensive antitumor activity. In this study, we constructed an RGD-modified bicistronic ING4/PTEN adenovirus (Ad.RGD-ING4-PTEN) and comprehensively investigated its effects following modification of the CNE human nasopharyngeal carcinoma cell line both in vitro and in vivo. We demonstrated that Ad.RGD-ING4-PTEN enhanced growth inhibition and apoptosis. Furthermore, expression of P21, Bax and cleaved caspase-3 was upregulated, while that of Bcl-2 and survivin was downregulated in CNE cells and CNE xenografted tumors. Moreover, Ad.RGD-ING4-PTEN treatment additively downregulated CD34, VEGF and microvessel density in subcutaneously (s.c.) xenografted CNE cell tumors. The enhanced antitumor activity generated by Ad.RGD-ING4-PTEN was closely associated with activation of the intrinsic and extrinsic apoptotic pathways and additive inhibition of tumor angiogenesis both in vitro and in vivo. On the basis of this evidence, it is believed that cancer gene therapy combining two tumor suppressors such as ING4 and PTEN can be used to establish an effective and novel therapeutic strategy for nasopharyngeal carcinoma and other cancers.
authors.affiliation: Department of ENT, The First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou 215006, P.R. China.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou 215006, P.R. China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Sheng
authors.affiliation: Institute for Cancer Center Laboratory, The First Affiliated Hospital and Experiment Center of Soochow University, Suzhou 215006, P.R. China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of ENT, The First Affiliated Hospital of Soochow University, Suzhou 215006, P.R. China.
authors.forename: Jisheng
authors.initials: J
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002277:Carcinoma; D018797:Cell Cycle Proteins / Q000235:genetics*; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009842:Oligopeptides / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019076:Transgenes; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D009842:Oligopeptides; D025521:Tumor Suppressor Proteins; C047981:arginyl-glycyl-aspartic acid; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human