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.


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.


CONCLUSIONS
These findings suggest that up-regulation of the iNOS gene may suppress the tumorigenicity and metastasis of oral cancer cells.
Harada
Koji
K
Second Department of Oral and Maxillofacial Surgery, University of Tokushima, School of Dentistry, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan. harako@dent.tokushima-u.ac.jp
Supriatno
Kawaguchi
Shin-Ichi
S
Tomitaro
Onoue
O
Yoshida
Hideo
H
Sato
Mitsunobu
M
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D009368:Neoplasm Transplantation; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse