title: Reexpression of human somatostatin receptor gene 2 gene mediated by oncolytic adenovirus increases antitumor activity of tumor necrosis factor-related apoptosis-inducing ligand against pancreatic cancer.
abstract: OBJECTIVE
  Pancreatic cancer continues to pose an enormous challenge to clinicians and cancer scientists. Clinical studies show that tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) exerts a potent and tumor-specific proapoptotic activity. However, most pancreatic cancer cells are resistant to TRAIL therapy. Human somatostatin receptor gene 2 (hSSTr2) is lost in 90% of pancreatic carcinoma. Oncolytic viruses are able to selectively lyse cancer cells and represent a promising novel anticancer therapy. Here, we investigated whether oncolytic adenovirus-mediated reexpression of hSSTr2 would enhance TRAIL-induced antitumor efficacy against pancreatic cancer.
  
  
  METHODS
  The antitumor efficacies of combined or single treatment of hSSTr2 and TRAIL mediated by oncolytic adenovirus were compared in pancreatic cancer cell culture and xenografts. The mechanisms involved in hSSTr2-induced sensitization to TRAIL were studied.
  
  
  RESULTS
  Oncolytic adenovirus-mediated reexpression of hSSTr2 potentiated TRAIL-induced tumor growth inhibition in vitro and in vivo. Reexpression of hSSTr2 augmented TRAIL-induced apoptosis against pancreatic cancer cells via up-regulation of death receptor 4 and down-regulation of Bcl-2.
  
  
  CONCLUSIONS
  hSSTr2 restoration mediated by oncolytic adenovirus enhances TRAIL-induced antitumor efficacy against pancreatic cancer. Combined treatment with oncolytic adenovirus-mediated hSSTr2 and TRAIL gene provides the rationale for a clinical trial in pancreatic cancer.
authors: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Zhenwei
authors: Z
authors: Zhang
authors: Yangbin
authors: Y
authors: Huang
authors: Kam
authors: K
authors: Newman
authors: Jinfa
authors: J
authors: Gu
authors: Xuemei
authors: X
authors: Zhang
authors: Hua
authors: H
authors: Wu
authors: Ming
authors: M
authors: Zhao
authors: Zhiqun
authors: Z
authors: Xianyu
authors: Xinyuan
authors: X
authors: Liu
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002277:Carcinoma / Q000235:genetics / Q000628:therapy*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000628:therapy*; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000502:physiology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000627:therapeutic use*; D014162:Transfection; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D017481:Receptors, Somatostatin; D053221:TNF-Related Apoptosis-Inducing Ligand; C093733:somatostatin receptor 2