title: ART1 silencing enhances apoptosis of mouse CT26 cells via the PI3K/Akt/NF-κB pathway.
abstract: OBJECTIVE
  Colorectal carcinoma is one of the most common cancers world-wide, with high morbidity and mortality rates. Arginine ADP-ribosyltransferase 1(ART1) is an important ecto-ADP-ribose transferase and has been proven to be intimately involved in a number of biological processes. However, the influence of ART1 on survival and apoptosis of colorectal carcinoma cells and the potential mechanism of action of ART1 remain uncharacterized.
  
  
  METHODS
  ART1 was silenced via lentiviral vector-mediated short hairpin RNA (shRNA) in CT26 colon carcinoma cells, and cisplatin (CDDP) was applied to induce apoptosis. Survival and apoptosis rate of CT26 cells was assessed by CCK8 assay, flow cytometry and Hoechst 33342 staining. Expression and activity of signaling proteins were detected by Western blot.
  
  
  RESULTS
  ART1 knockdown enhanced the inhibition of cell survival and increased the apoptosis induced by CDDP. Furthermore, the reduced survival rate correlated with reduced levels of phos-Akt(Thr308) and phos-IκBα and reduced NF-κB p65 nuclear translocation. A decline in Bcl-2 and Bcl-xl expression and an increase in Bax expression may explain the enhanced apoptosis.
  
  
  CONCLUSIONS
  This study provides a molecular mechanism for the function of ART1 in colorectal carcinoma and defines a potential therapeutic target for the enhanced treatment of this prominent world-wide disease.
authors: Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
authors: Ming
authors: M
authors: Xiao
authors: Yi
authors: Y
authors: Tang
authors: Ya-Lan
authors: YL
authors: Wang
authors: Lian
authors: L
authors: Yang
authors: Xian
authors: X
authors: Li
authors: Jing
authors: J
authors: Kuang
authors: Guang-Lin
authors: GL
authors: Song
mesh_terms: D036002:ADP Ribose Transferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D036002:ADP Ribose Transferases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin