[Arginase inhibitor nor-NOHA induces apoptosis and inhibits invasion and migration of HepG2 cells]

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017 Apr;33(4):477-482.
[Article in Chinese]

Abstract

Objective To investigate the cell inhibitory effect of arginase inhibitor nor-NOHA on HepG2 hepatocellular carcinoma cells and related mechanism. Methods CCK-8 assay was used to detect the cell proliferation and flow cytometry to detect the apoptosis of HepG2 cells treated with (0, 0.5, 1.0, 2.0, 3.0) ng/μL nor-NOHA. The protein levels of arginase 1 (Arg1), P53, matrix metalloproteinase-2 (MMP-2), E-cadherin (ECD) were determined by Western blotting. Real time quantitative PCR was employed to examine the changes in the mRNA level of inducible nitric oxide synthase (iNOS). Griess assay was used to measure the concentration of nitric oxide (NO) in HepG2 cells. TranswellTM assay and wound-healing assay were performed to evaluate the changes of the cell invasion and migration ability, respectively. Results nor-NOHA inhibited the proliferation and induced the apoptosis of HepG2 cells. It also decreased the expression levels of Arg1 and MMP-2, increased the expression levels of P53 and ECD as well as the production of NO; in addition, nor-NOHA inhibited the invasion and migration of HepG2 cells. Conclusion Nor-NOHA can induce cell apoptosis and inhibit the ability of invasion and migration of HepG2 cells by inhibiting Arg1, which is related with the increase of iNOS expression and the high concentration of NO.

MeSH terms

  • Apoptosis / drug effects*
  • Arginase / antagonists & inhibitors*
  • Arginase / genetics
  • Arginase / metabolism
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Enzyme Inhibitors / pharmacology*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / physiopathology*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Neoplasm Invasiveness
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism

Substances

  • Enzyme Inhibitors
  • N(omega)-hydroxynorarginine
  • Arginine
  • Nitric Oxide Synthase Type II
  • Matrix Metalloproteinase 2
  • ARG1 protein, human
  • Arginase