title: Nicotinamide prohibits proliferation and enhances chemosensitivity of pancreatic cancer cells through deregulating SIRT1 and Ras/Akt pathways.
abstract: BACKGROUND
  Nicotinamide (NAM), the precursor for the synthesis of NAD(+) and also an inhibitor of SIRT1, has been discovered to inhibit some types of cancer. However, little is known about the effects of NAM on pancreatic cancer cells. Since previous research showed that SIRT1 and K-Ras/Akt signaling acted as a promoter in tumorigenesis of pancreatic cancer, our present research set out to explore whether NAM inhibits proliferation and facilitates chemosensitivity in pancreatic cancer cells as well as the potential mechanisms involving SIRT1 and K-Ras/Akt pathway.
  
  
  METHODS
  Cell viability was assessed by MTT assay, and apoptosis and cell cycle were measured by flow cytometry. Cell invasive ability was evaluated by matrigel invasion assays. The activity of SIRT1 was measured by the Fluor de Lys deacetylation assay. Expression levels of SIRT1, K-Ras, Phosphated Akt (P-Akt, Ser-473) and Akt were measured using western blot. In vivo tumor growth was performed in pancreatic cancer cells xenografts.
  
  
  RESULTS
  NAM inhibited the proliferation of pancreatic cancer cells in a dose-dependent manner, and significantly induced apoptosis and cell cycle arrest in G2/M phase. Moreover, NAM obviously restrained cell invasive ability and increased the chemosensitivity. NAM significantly inhibited the activity of SIRT1 and decreased expression of SIRT1, K-Ras and P-Akt. Further, NAM prohibited proliferation and enhanced GEM antitumor activity in vivo.
  
  
  CONCLUSIONS
  Our results implied that NAM might be a potential therapeutic agent for human pancreatic cancer treatment through downregulating SIRT1, K-Ras and P-Akt expression.
authors.affiliation: Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Jun-gang
authors.initials: JG
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Qi
authors.initials: Q
authors.lastname: Qin
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Shi-chang
authors.initials: SC
authors.lastname: Deng
authors.forename: Kui
authors.initials: K
authors.lastname: Tian
authors.forename: Chun-you
authors.initials: CY
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D011905:Genes, ras / Q000502:physiology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D009536:Niacinamide / Q000008:administration & dosage / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009536:Niacinamide; D051057:Proto-Oncogene Proteins c-akt; C447939:SIRT1 protein, human; D056564:Sirtuin 1