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

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

doi:10.3892/ol.2019.10975

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

Authors:
- Hisato Yoshida
- Hitoshi Yoshimura
- Shinpei Matsuda
- Satoshi Yamamoto
- Masahiro Ohmori
- Keiichi Ohta
- Takashi Ryoke
- Hayato Itoi
- Tamotsu Kiyoshima
- Motohiro Kobayashi
- Kazuo Sano
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Affiliations: Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910‑1193, Japan, Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812‑8582, Japan, Department of Tumor Pathology, Unit of Pathological Sciences, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910‑1193, Japan
Published online on: October 10, 2019 https://doi.org/10.3892/ol.2019.10975
Pages: 5793-5800
Copyright: © Yoshida et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Neville BW and Day TA: Oral cancer and precancerous lesions. CA Cancer J Clin. 52:195–215. 2002. View Article : Google Scholar : PubMed/NCBI
3	Marta GN, Riera R, Bossi P, Zhong LP, Licitra L, Macedo CR, de Castro Junior G, Carvalho AL, William WN Jr and Kowalski LP: Induction chemotherapy prior to surgery with or without postoperative radiotherapy for oral cavity cancer patients: Systematic review and meta-analysis. Eur J Cancer. 51:2596–2603. 2015. View Article : Google Scholar : PubMed/NCBI
4	Javed F and Warnakulasuriya S: Is there a relationship between periodontal disease and oral cancer? A systematic review of currently available evidence. Crit Rev Oncol Hematol. 97:197–205. 2016. View Article : Google Scholar : PubMed/NCBI
5	Jain S and Darveau RP: Contribution of Porphyromonas gingivalis lipopolysaccharide to periodontitis. Periodontol 2000. 54:53–70. 2010. View Article : Google Scholar : PubMed/NCBI
6	Yang H, Wang B, Wang T, Xu L, He C, Wen H, Yan J, Su H and Zhu X: Toll-like receptor 4 prompts human breast cancer cells invasiveness via lipopolysaccharide stimulation and is overexpressed in patients with lymph node metastasis. PLoS One. 9:e1099802014. View Article : Google Scholar : PubMed/NCBI
7	He Z, Deng R, Huang X, Ni Y, Yang X, Wang Z and Hu Q: Lipopolysaccharide enhances OSCC migration by promoting epithelial-mesenchymal transition. J Oral Pathol Med. 44:685–692. 2015. View Article : Google Scholar : PubMed/NCBI
8	Liu CH, Chang SH, Narko K, Trifan OC, Wu MT, Smith E, Haudenschild C, Lane TF and Hla T: Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem. 276:18563–18569. 2001. View Article : Google Scholar : PubMed/NCBI
9	Kojima M, Morisaki T, Izuhara K, Uchiyama A, Matsunari Y, Katano M and Tanaka M: Lipopolysaccharide increases cyclo-oxygenase-2 expression in a colon carcinoma cell line through nuclear factor-kappa B activation. Oncogene. 19:1225–1231. 2000. View Article : Google Scholar : PubMed/NCBI
10	Gallo O, Franchi A, Magnelli L, Sardi I, Vannacci A, Boddi V, Chiarugi V and Masini E: Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis. Neoplasia. 3:53–61. 2001. View Article : Google Scholar : PubMed/NCBI
11	Chan G, Boyle JO, Yang EK, Zhang F, Sacks PG, Shah JP, Edelstein D, Soslow RA, Koki AT, Woerner BM, et al: Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. Cancer Res. 59:991–994. 1999.PubMed/NCBI
12	Gallo O, Masini E, Bianchi B, Bruschini L, Paglierani M and Franchi A: Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma. Hum Pathol. 33:708–714. 2002. View Article : Google Scholar : PubMed/NCBI
13	Shin DM, Zhang H, Saba NF, Chen AY, Nannapaneni S, Amin AR, Müller S, Lewis M, Sica G, Kono S, et al: Chemoprevention of head and neck cancer by simultaneous blocking of epidermal growth factor receptor and cyclooxygenase-2 signaling pathways: Preclinical and clinical studies. Clin Cancer Res. 19:1244–1256. 2013. View Article : Google Scholar : PubMed/NCBI
14	Chiang SL, Velmurugan BK, Chung C, Lin SH, Wang ZH, Hua CH, Tsai MH, Kuo TM, Yeh KT, Chang PY, et al: Preventive effect of celecoxib use against cancer progression and occurrence of oral squamous cell carcinoma. Sci Rep. 7:62352017. View Article : Google Scholar : PubMed/NCBI
15	Xu XF, Xie CG, Wang XP, Liu J, Yu YC, Hu HL and Guo CY: Selective inhibition of cyclooxygenase-2 suppresses the growth of pancreatic cancer cells in vitro and in vivo. Tohoku J Exp Med. 215:149–157. 2008. View Article : Google Scholar : PubMed/NCBI
16	Yoshida H, Yoshimura H, Matsuda S, Ryoke T, Kiyoshima T, Kobayashi M and Sano K: Effects of peritumoral bevacizumab injection against oral squamous cell carcinoma in a nude mouse xenograft model: A preliminary study. Oncol Lett. 15:8627–8634. 2018.PubMed/NCBI
17	National Research Council, . Guide for the Care and Use of Laboratory Animals8th. The National Academies Press; Washington, DC: 2011
18	Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ and Lee JO: Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell. 130:906–917. 2007. View Article : Google Scholar : PubMed/NCBI
19	Lu YC, Yeh WC and Ohashi PS: LPS/TLR4 signal transduction pathway. Cytokine. 42:145–151. 2008. View Article : Google Scholar : PubMed/NCBI
20	Abrahão AC, Giudice FS, Sperandio FF and Pinto Junior Ddos S: Effects of celecoxib treatment over the AKT pathway in head and neck squamous cell carcinoma. J Oral Pathol Med. 42:793–798. 2013. View Article : Google Scholar : PubMed/NCBI
21	Kwak YE, Jeon NK, Kim J and Lee EJ: The cyclooxygenase-2 selective inhibitor celecoxib suppresses proliferation and invasiveness in the human oral squamous carcinoma. Ann N Y Acad Sci. 1095:99–112. 2007. View Article : Google Scholar : PubMed/NCBI
22	Li WZ, Wang XY, Li ZG, Zhang JH and Ding YQ: Celecoxib enhances the inhibitory effect of cisplatin on Tca8113 cells in human tongue squamous cell carcinoma in vivo and in vitro. J Oral Pathol Med. 39:579–584. 2010.PubMed/NCBI
23	Grösch S, Tegeder I, Niederberger E, Bräutigam L and Geisslinger G: COX-2 independent induction of cell cycle arrest and apoptosis in colon cancer cells by the selective COX-2 inhibitor celecoxib. FASEB J. 15:2742–2744. 2001. View Article : Google Scholar : PubMed/NCBI
24	Patil VM, Noronha V, Joshi A, Muddu VK, Dhumal S, Bhosale B, Arya S, Juvekar S, Banavali S, D'Cruz A, et al: A prospective randomized phase II study comparing metronomic chemotherapy with chemotherapy (single agent cisplatin), in patients with metastatic, relapsed or inoperable squamous cell carcinoma of head and neck. Oral Oncol. 51:279–286. 2015. View Article : Google Scholar : PubMed/NCBI
25	Argiris A, Li Y, Murphy BA, Langer CJ and Forastiere AA: Outcome of elderly patients with recurrent or metastatic head and neck cancer treated with cisplatin-based chemotherapy. J Clin Oncol. 22:262–268. 2004. View Article : Google Scholar : PubMed/NCBI
26	Kawano S, Zheng Y, Oobu K, Matsubara R, Goto Y, Chikui T, Yoshitake T, Kiyoshima T, Jinno T, Maruse Y, et al: Clinicopathological evaluation of pre-operative chemoradiotherapy with S-1 as a treatment for locally advanced oral squamous cell carcinoma. Oncol Lett. 11:3369–3376. 2016. View Article : Google Scholar : PubMed/NCBI
27	Gartel AL and Tyner AL: The role of the cyclin-dependent kinase inhibitor p21 in apoptosis. Mol Cancer Ther. 1:639–649. 2002.PubMed/NCBI
28	Lai FB, Liu WT, Jing YY, Yu GF, Han ZP, Yang X, Zeng JX, Zhang HJ, Shi RY, Li XY, et al: Lipopolysaccharide supports maintaining the stemness of CD133(+) hepatoma cells through activation of the NF-κB/HIF-1α pathway. Cancer Lett. 378:131–141. 2016. View Article : Google Scholar : PubMed/NCBI
29	Li S, Xu X, Jiang M, Bi Y, Xu J and Han M: Lipopolysaccharide induces inflammation and facilitates lung metastasis in a breast cancer model via the prostaglandin E2-EP2 pathway. Mol Med Rep. 11:4454–4462. 2015. View Article : Google Scholar : PubMed/NCBI
30	Xue WP, Bai SM, Luo M, Bi ZF, Liu YM and Wu SK: Phase I clinical trial of nasopharyngeal radiotherapy and concurrent celecoxib for patients with locoregionally advanced nasopharyngeal carcinoma. Oral Oncol. 47:753–757. 2011. View Article : Google Scholar : PubMed/NCBI
31	Cerchietti LC, Bonomi MR, Navigante AH, Castro MA, Cabalar ME and Roth BM: Phase I/II study of selective cyclooxygenase-2 inhibitor celecoxib as a radiation sensitizer in patients with unresectable brain metastases. J Neurooncol. 71:73–81. 2005. View Article : Google Scholar : PubMed/NCBI