Overexpression of iNOS Gene Suppresses the Tumorigenicity and Metastasis of Oral Cancer Cells

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. Nitric oxide (NO), a free-radical gas, is a short-living molecule which is involved in a multitude of biological processes including inflammation and cancer (1). NO can react with other radicals to form cytotoxic compounds, such