Author(s)

Naoki Anbo, Kazuhiro Ogi, Yohei Sogabe, Makoto Shimanishi, Takeshi Kaneko, Hironari Dehari, Akihiro Miyazaki, Hiroyoshi Hiratsuka

Department of Oral Surgery, School of Medicine, Sapporo Medical University, Sapporo, Japan.

Object: Hypoxia occurs when oxygen tension drops below normal limits, and malignant tumors often experience hypoxia, which activates the expression of genes through oxygen-sensitive transcription factors, including the hypoxiainducible factor (HIF) and the nuclear factor-κB (NF-κB). NF-κB pathway represents an attractive therapeutic target in both cancer cells and ischemic cells, which involves immune response. To investigate the expression of NF-κB target genes in oral squamous cancer carcinoma (OSCC) under hypoxia, we performed cDNA plate array analyses of 23 NF-κB-regulated genes in different cell lines. Our aim was to clarify the functions of NF-κB in OSCC under hypoxia. Results: We conducted an NF-κB reporter assay to examine NF-κB activation under hypoxia. This luciferase-based reporter assay showed that hypoxia induced NF-κB activation after 24 h of hypoxia. We also found that vascular endothelial growth factor-C (VEGF-C) of NF-κB-regulated genes was upregulated in both cell lines under hypoxia. We then tested the influence of NF-κB/p65 knockdown on these cells and NF-κB/p65 knockdown inhibited the proliferation of OSCC cells by colony assay. Conclusion: Based on these findings, we postulate that one mechanism by which hypoxic OSCC cells may involve NF-κB-mediated upregulation. Our results also indicate that the knockdown of NF-κB/p65 subunit lead to growth inhibition during hypoxia in OSCC cells. These results suggest that knockdown of NF-κB/p65 subunit could be a potential therapeutic option for patients with OSCC.

Oral Squamous Cell Carcinoma; Hypoxia; NF-κB

N. Anbo, K. Ogi, Y. Sogabe, M. Shimanishi, T. Kaneko, H. Dehari, A. Miyazaki and H. Hiratsuka, "Suppression of NF-κB/p65 Inhibits the Proliferation in Oral Squamous Cancer Cells," Journal of Cancer Therapy, Vol. 4 No. 4, 2013, pp. 891-897. doi: 10.4236/jct.2013.44100.