Glutamate dehydrogenase inhibits tumor growth in gastric cancer through the Notch signaling pathway

Cancer Biomark. 2019;26(3):303-312. doi: 10.3233/CBM-190022.

Abstract

Glutamate dehydrogenase (GDH) is a key enzyme in glutaminolysis and can regulate allosteric functions. Immunohistochemical study found that GDH expressed in gastric cancer cell cytoplasm and membrane, and a few located in the nucleus, ranging from light yellow to tan to sepia. According to the analysis by Kaplan Meier survival curve and the Log-Rank test, the median survival of GDH high expression in patients was 51.7 months with 95% confidence intervals (CI) was 41.138-55.262. The expression level of GDH was significantly reduced after silencing GDH gene in gastric cancer cells and tissues. Further, after silencing GDH gene, gastric cancer cell migration and invasion ability were decreased significantly. Protein expression of. In addition, tumor growth was significantly reduced after silencing GDH gene. In vivo and in vitro experiments suggest that GDH can decrease gastric cancer cell migration and invasion, thus inhibiting tumor growth.

Keywords: Glutamate dehydrogenase; gastric cancer cell; invasion; migration; notch signaling pathways.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Follow-Up Studies
  • Gastrectomy
  • Gene Silencing
  • Glutamate Dehydrogenase / genetics
  • Glutamate Dehydrogenase / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Middle Aged
  • RNA, Small Interfering / metabolism
  • Receptors, Notch / metabolism*
  • Signal Transduction / genetics
  • Stomach / pathology
  • Stomach / surgery
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / surgery
  • Xenograft Model Antitumor Assays
  • Young Adult

Substances

  • Biomarkers, Tumor
  • RNA, Small Interfering
  • Receptors, Notch
  • Glutamate Dehydrogenase
  • GLUD1 protein, human