Overexpression of iNOS gene suppresses the tumorigenicity and metastasis of oral cancer cells

In Vivo. Jul-Aug 2004;18(4):449-55.

Abstract

Background: The inducible nitric oxide synthase (iNOS) is associated with inflammatory processes and cancer formation through production of nitric oxide (NO). However, the clinical importance of the expression of iNOS in oral cancer remains unclear. In the present study, we examined whether up-regulation of the iNOS gene can affect growth and metastasis of an oral cancer cell line (B88t cell) in vitro and in vivo.

Materials and methods: We constructed an expression vector containing sense-oriented murine iNOS cDNA with pcDNA3.1. We transfected B88t cells with the sense expression vector to up-regulate the expression of the iNOS gene in the sense transfectants.

Results: The expression of iNOS protein was up-regulated in the sense transfectants and that up-regulation of the iNOS gene exerted a growth inhibitory effect on B88t cells in vitro and in vivo. Moreover, up-regulation of the iNOS gene markedly inhibited the migration of cancer cells in a Boyden chamber. Furthermore, up-regulation of the iNOS gene dramatically inhibited metastases to the cervical lymph node in vivo.

Conclusion: These findings suggest that up-regulation of the iNOS gene may suppress the tumorigenicity and metastasis of oral cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / secondary*
  • Cell Movement
  • Gene Expression Regulation, Neoplastic*
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mouth Neoplasms / enzymology
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / pathology*
  • Neoplasm Transplantation
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Transfection
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse