論文

査読有り 国際誌
2019年12月

Celecoxib suppresses lipopolysaccharide-stimulated oral squamous cell carcinoma proliferation in vitro and in vivo.

Oncology letters
  • Hisato Yoshida
  • ,
  • Hitoshi Yoshimura
  • ,
  • Shinpei Matsuda
  • ,
  • Satoshi Yamamoto
  • ,
  • Masahiro Ohmori
  • ,
  • Keiichi Ohta
  • ,
  • Takashi Ryoke
  • ,
  • Hayato Itoi
  • ,
  • Tamotsu Kiyoshima
  • ,
  • Motohiro Kobayashi
  • ,
  • Kazuo Sano

18
6
開始ページ
5793
終了ページ
5800
記述言語
英語
掲載種別
DOI
10.3892/ol.2019.10975

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.

リンク情報
DOI
https://doi.org/10.3892/ol.2019.10975
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31788052
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865759