title: Adenoviral-mediated gene transfer of Gadd45a results in suppression by inducing apoptosis and cell cycle arrest in pancreatic cancer cell.
abstract: BACKGROUND
  The extremely poor prognosis of patients with pancreatic ductal adenocarcinoma indicates the need for novel therapeutic approaches. The growth arrest and DNA damage-inducible (Gadd) gene Gadd45a is a member of a group of genes that are induced by DNA damaging agents and growth arrest signals.
  
  
  METHODS
  We evaluated the biological activity of Gadd45a in pancreatic ductal adenocarcinoma cancer-derived cell lines and assessed the efficacy of a combined treatment with adenoviral-mediated expression of Gadd45a (Ad-G45a) and anticancer drug (Etoposide, cisplatin, 5-fluorouracil, respectively) for the PANC1 cell line.
  
  
  RESULTS
  Gadd45a is variously expressed in cell lines derived from pancreatic ductal adenocarcinoma cancer and adenoviral-mediated expression of Gadd45a (Ad-G45a) in these cells results in apoptosis via caspase activation and cell-cycle arrest in the G2/M phase. Gadd45a significantly increased the chemosensitivity of PANC1, which may be due to abundant apoptosis induction and cell cycle arrest. By combinational treatment of Ad-G45a infection and chemotherapeutics, Gadd45a expression was elevated to a higher extent in cancer cells with wild-type p53 than in that with knocked-out p53 status, indicating a higher chemosensitivity to cancer chemotherapy.
  
  
  CONCLUSIONS
  Gadd45a may be a promising candidate for use in cancer gene therapy in combination with chemotherapeutic agents.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Li
authors.forename: Haili
authors.initials: H
authors.lastname: Qian
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Haijuan
authors.initials: H
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.forename: Ming
authors.initials: M
authors.lastname: Fu
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle / Q000235:genetics*; D002465:Cell Movement; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D000097642:GADD45 Proteins
chemical_list: D002945:Cisplatin; D005047:Etoposide; D005472:Fluorouracil; D047908:Intracellular Signaling Peptides and Proteins; D000097642:GADD45 Proteins