Celecoxib suppresses lipopolysaccharide‑stimulated oral squamous cell carcinoma proliferation in�vitro and in�vivo

Abstract

Periodontitis is one of the most common chronic oral inflammatory conditions worldwide and is associated with a risk of developing oral squamous cell carcinoma (OSCC). Porphyromonas gingivalis is a major pathogen in periodontitis, and its lipopolysaccharide (LPS) promotes the expression of cyclooxygenase-2 (COX-2) in OSCC both in vivo and in vitro. Celecoxib is a selective COX-2 inhibitor; however, its antitumor effects on P. gingivalis LPS-stimulated OSCC and the underlying molecular mechanism remain unclear. To elucidate the association between periodontitis and OSCC, the effect of P. gingivalis-derived LPS on OSCC cell proliferation was examined both in vitro and in vivo in the present study. The expression levels of COX-2 and p53 in OSCC cells with/without celecoxib treatment were determined via western blotting. The therapeutic potential of celecoxib in LPS-stimulated OSCC was evaluated by staining for Ki-67 and p21, as well as with terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining. LPS treatment significantly increased OSCC cell proliferation in vitro, and celecoxib significantly inhibited cell proliferation with/without LPS treatment. Celecoxib treatment of OSCC cells downregulated the protein expression levels of COX-2 compared with untreated cells, but there was little change in p53 expression. In the mouse xenograft model, oral administration of celecoxib significantly suppressed tumor growth, reduced the expression of Ki-67, increased the apoptosis index and induced p21 expression with/without LPS treatment. The results from the present study demonstrate that P. gingivalis' LPS can stimulate tumor growth by interacting with OSCC cells. In conclusion, these results suggest that celecoxib could be used for the effective prevention and treatment of LPS-stimulated OSCC.

Impact of cytotoxic chemotherapy on aldo-keto reductase family 1 member B10 expression

“…Likewise, Yoshida et al. 20 noted that 5.1% of patients treated with proton beam radiotherapy for hepatocellular carcinoma developed an alpha-fetoprotein spike at a median of 1 month.…”

The molecular mechanisms of celecoxib in tumor development

“…[ 51 52 ] In the study of squamous cell carcinoma of head and neck, it was found that lipopolysaccharide in Porphyromonas gingivalis (the main pathogen of periodontitis) promotes the expression of COX-2 in oral squamous cell carcinoma, while celecoxib can significantly inhibit the development of tumor, and inhibit the transformation of G0/G1-S phase and reduce the proliferation of tumor cells by increasing the expression of p21. [ 53 54 ] Furthermore, celecoxib can promote T cells to play a role in the tumor microenvironment through the COX-2 pathway. Since 2,3-dioxygenase (IDO) can decompose L-tryptophan into L-kynurenine, a large amount of IDO decomposition of tryptophan in the tumor microenvironment will cause immune T lymphocytes to not effectively recognize tumor cells, and even accelerate T lymphocyte apoptosis.…”

The Efficacy and Safety of Celecoxib in Addition to Standard Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Numerous studies have reported the chemopreventive efficacy of celecoxib in several precancerous lesions and cancer types, including colon polyp, colorectal adenomas, lung cancer, and prostate cancer [ 13 , 14 , 15 , 16 , 17 ]. Furthermore, celecoxib was found to prevent tumor growth through multiple pathways and targets [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. In terms of the molecular mechanism of celecoxib, it can regulate FAK, Cx43, p21, and Ki-67 molecules, and block AKT activation [ 20 , 22 , 24 ], which can inhibit tumor cell proliferation and induce apoptosis.…”

“…Furthermore, celecoxib was found to prevent tumor growth through multiple pathways and targets [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. In terms of the molecular mechanism of celecoxib, it can regulate FAK, Cx43, p21, and Ki-67 molecules, and block AKT activation [ 20 , 22 , 24 ], which can inhibit tumor cell proliferation and induce apoptosis. Moreover, celecoxib is involved in ERK1/2 MAPK and PI3K/AKT pathways, exerting an antiangiogenic effect [ 18 , 23 ].…”