Increased expression of Cox-2 has been found in a variety of human malignancies, including HNSCC [14–16]. Previous studies have reported several mechanisms by which Cox-2 contributes to carcinogenesis as well as cancer progression, including the activation of carcinogens [17], resistance to apoptosis find more [18, 19], immunosuppression [20, 21], the promotion of angiogenesis [11, 22], the stimulation of proliferation [23] and invasiveness [24], and the autocrine

activity of estrogen [25]. Such a multifaceted function of Cox-2 in conferring the malignant phenotype strongly suggested that Cox-2 is an attractive preventive and therapeutic target for various cancers [12, 13, 26–29]. A number of clinical trials have been carried out to examine the benefit of Cox-2 inhibitors, such as celecoxib,

in the chemoprevention of premalignant lesions such as familial adenoma Evofosfamide polyposis (FAP) [30], Barrett’s esophagus [31], and oral premalignant lesions [32], as well as in the treatment of advanced cancers in combination with chemotherapy [33–36]. However, these trials could demonstrate neither a significant chemopreventive effect nor any additional therapeutic Ruxolitinib molecular weight effect of celecoxib on clinical outcomes, except in FAP, suggesting that the optimal applications of Cox-2 inhibitors should be reconsidered, and that further research is necessary regarding the various mechanisms underlying the anti-cancer effects of Cox-2 inhibitors against tumors. An inverse SB-3CT relationship between E-cadherin and Cox-2 and its molecular mechanism in cancer cells was first shown in non-small cell lung cancer (NSCLC), in which Cox-2 overexpression led to decreased E-cadherin expression through the upregulation of PGE2 and transcriptional repressors of E-cadherin, whereas the inhibition of Cox-2 showed an inverse regulation of those molecules [37].

A similar effect of Cox-2 inhibitors that reverse the EMT by restoring E-cadherin expression was also found in subsets of colon, gastric, and bladder cancer cells [38–43]. However, in HNSCC, neither the effect of Cox-2 inhibitors on the regulation of E-cadherin expression nor its specific mechanism has been examined to date, except for a study that investigated interleukin-1β (IL-1β)-induced upregulation of Snail leading to EMT [44]. We conducted the present study to determine whether selective Cox-2 inhibitors restore the expression of E-cadherin through the downregulation of its transcriptional repressors to suppress the EMT in HNSCC cells, and to determine whether the gene expression levels of the molecules that are implicated in the EMT are correlated with clinicopathological parameters in HNSCC.