Overexpression of Nampt in gastric cancer and chemopotentiating effects of the Nampt inhibitor FK866 in combination with fluorouracil

Oncol Rep. 2011 Nov;26(5):1251-7. doi: 10.3892/or.2011.1378. Epub 2011 Jul 4.


Nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in the NAD⁺ salvage pathway, is over-expressed and important in the carcinogenesis in several types of cancers. The expression of Nampt and its role in gastric cancer remain largely unknown. In this study, using real-time PCR and Western blotting we found that Nampt was overexpressed at the mRNA and protein levels, respectively, in established gastric cancer cells and human gastric cancer tissues. The specific Nampt inhibitor FK866 repressed gastric cancer cell proliferation, as assessed by MTT assay. Using transwell and soft agar clonogenic assays, we also found that FK866 suppressed gastric cancer cell migration and anchorage-independent growth, respectively. These inhibitory effects of FK866 were accompanied by significantly decreased expression of VEGF, MMP2, MMP9 and NF-κB. As determined by MTT assay and flow cytometry, FK866 also increased the chemo-sensitivity of gastric cancer cells to fluorouracil by greater inhibition of cell proliferation and the induction of apoptosis. Our findings indicate that Nampt may be a new therapeutic target for gastric cancer.

MeSH terms

  • Acrylamides / pharmacology*
  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Drug Synergism
  • Fluorouracil / pharmacology*
  • Humans
  • Nicotinamide Phosphoribosyltransferase / antagonists & inhibitors*
  • Nicotinamide Phosphoribosyltransferase / biosynthesis*
  • Nicotinamide Phosphoribosyltransferase / genetics
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Piperidines / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology


  • Acrylamides
  • Antimetabolites, Antineoplastic
  • N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide
  • Piperidines
  • RNA, Messenger
  • Nicotinamide Phosphoribosyltransferase
  • Fluorouracil