Cyclooxygenase-2 expression is suppressed by eicosapentaenoic acid and is a prognostic factor for esophageal squamous cell carcinoma patients after curative surgery

Main Article Content

Koji Mizoguchi Hideyuki Ishiguro Ryo Ogawa Tatsuya Tanaka Hiroyuki Sagawa Tomotaka Okubo Yosuke Samoto

Abstract

Background/Purpose

We showed that eicosapentaenoic acid (EPA) stimulated apoptosis via caspases in ESCC cell lines, indicating an anti-cancer effect. In the present study, we aimed to clarify whether the anticancer and anti-inflammatory actions of EPA are related to COX-2.

Materials and method

We performed immunohistochemical analysis in 92 ESCC specimens to investigate the relationship between COX-2 expression and prognosis, and Western blotting in ESCC cell lines to determine whether EPA suppresses COX-2.

Results

Immunohistochemistry showed that COX-2 expression levels were enhanced in the ESCC specimens, with a significant prognostic impact on the survival of surgically treated cases (P=0.0017, log-rank test). Multivariate analysis showed that the prognostic impact of COX-2 is independent of disease stage (P=0.02). Western blotting revealed that the KYSE180 and TE11 ESCC cell lines express COX-2, which was greatly suppressed by EPA stimulation.

Conclusions

The expression of COX-2 in patients with ESCC is associated with significantly poor survival rates. EPA may have an anti-cancer effect via suppression of COX-2.

Article Details

How to Cite
MIZOGUCHI, Koji et al. Cyclooxygenase-2 expression is suppressed by eicosapentaenoic acid and is a prognostic factor for esophageal squamous cell carcinoma patients after curative surgery. Medical Research Archives, [S.l.], v. 5, n. 3, mar. 2017. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/1024>. Date accessed: 29 mar. 2024.
Keywords
cyclooxygenase-2, eicosapentaenoic acid, esophageal squamous cell carcinoma, immunohistochemistry,  prognosis
Section
Research Articles

References

Das, U. N. (2006). Essential fatty acids: biochemistry, physiology and pathology. Biotechnol J, 1(4), 420-439. doi: 10.1002/biot.200600012
Eser, P. O., Vanden Heuvel, J. P., Araujo, J., & Thompson, J. T. (2013). Marine- and plant-derived omega-3 fatty acids differentially regulate prostate cancer cell proliferation. Mol Clin Oncol, 1(3), 444-452. doi: 10.3892/mco.2013.76
Fietkau, R., Lewitzki, V., Kuhnt, T., Holscher, T., Hess, C. F., Berger, B., . . . Lubgan, D. (2013). A disease-specific enteral nutrition formula improves nutritional status and functional performance in patients with head and neck and esophageal cancer undergoing chemoradiotherapy: results of a randomized, controlled, multicenter trial. Cancer, 119(18), 3343-3353. doi: 10.1002/cncr.28197
Fujita, T., Daiko, H., & Nishimura, M. (2012). Early enteral nutrition reduces the rate of life-threatening complications after thoracic esophagectomy in patients with esophageal cancer. Eur Surg Res, 48(2), 79-84. doi: 10.1159/000336574
Hamai, Y., Hihara, J., Emi, M., Taomoto, J., Aoki, Y., Kishimoto, I., . . . Okada, M. (2013). Treatment outcomes and prognostic factors for thoracic esophageal cancer with clinical evidence of adjacent organ invasion. Anticancer Res, 33(8), 3495-3502.
Hawcroft, G., Volpato, M., Marston, G., Ingram, N., Perry, S. L., Cockbain, A. J., . . . Hull, M. A. (2012). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid inhibits mouse MC-26 colorectal cancer cell liver metastasis via inhibition of PGE2-dependent cell motility. Br J Pharmacol, 166(5), 1724-1737. doi: 10.1111/j.1476-5381.2012.01882.x
Hofstetter, W., Swisher, S. G., Correa, A. M., Hess, K., Putnam, J. B., Jr., Ajani, J. A., . . . Roth, J. A. (2002). Treatment outcomes of resected esophageal cancer. Ann Surg, 236(3), 376-384; discussion 384-375. doi: 10.1097/01.SLA.0000027925.23604.5C
Isono, K., Sato, H., & Nakayama, K. (1991). Results of a nationwide study on the three-field lymph node dissection of esophageal cancer. Oncology, 48(5), 411-420.
Kanda, Y. (2013). Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant, 48(3), 452-458. doi: 10.1038/bmt.2012.244
Kobayashi, T., Oshima, K., Yokobori, T., Idetsu, A., Hayashi, Y., Hinohara, R. N., . . . Kuwano, H. (2013). Perioperative nutriture in esophageal cancer patients undergoing esophagectomy. Hepatogastroenterology, 60(126), 1311-1316. doi: 10.5754/hge11257
Mizoguchi, K., Ishiguro, H., Kimura, M., Takahashi, H., Sakamoto, N., Tanaka, T., & Takeyama, H. (2014). Induction of apoptosis by eicosapentaenoic acid in esophageal squamous cell carcinoma. Anticancer Res, 34(12), 7145-7149.
Nakanishi, M., Perret, C., Meuillet, E. J., & Rosenberg, D. W. (2015). Non-cell autonomous effects of targeting inducible PGE2 synthesis during inflammation-associated colon carcinogenesis. Carcinogenesis, 36(4), 478-486. doi: 10.1093/carcin/bgv004
Nozoe, T., Ezaki, T., Kabashima, A., Baba, H., & Maehara, Y. (2005). Significance of immunohistochemical expression of cyclooxygenase-2 in squamous cell carcinoma of the esophagus. Am J Surg, 189(1), 110-115. doi: 10.1016/j.amjsurg.2004.03.019
Oyama, K., Fujimura, T., Ninomiya, I., Miyashita, T., Kinami, S., Fushida, S., . . . Koichi, M. (2005). A COX-2 inhibitor prevents the esophageal inflammation-metaplasia-adenocarcinoma sequence in rats. Carcinogenesis, 26(3), 565-570. doi: 10.1093/carcin/bgh340
Pisani, P., Parkin, D. M., Bray, F., & Ferlay, J. (1999). Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer, 83(1), 18-29.
Sio, T. T., Wilson, Z. C., Stauder, M. C., Bhatia, S., Martenson, J. A., Quevedo, J. F., . . . Miller, R. C. (2016). Long-term Treatment Outcomes for Locally Advanced Esophageal Cancer: A Single-Institution Experience. Am J Clin Oncol, 39(5), 448-452. doi: 10.1097/COC.0000000000000089
Sivula, A., Buskens, C. J., van Rees, B. P., Haglund, C., Offerhaus, G. J., van Lanschot, J. J., & Ristimaki, A. (2005). Prognostic role of cyclooxygenase-2 in neoadjuvant-treated patients with squamous cell carcinoma of the esophagus. Int J Cancer, 116(6), 903-908. doi: 10.1002/ijc.21134
Slagsvold, J. E., Pettersen, C. H., Follestad, T., Krokan, H. E., & Schonberg, S. A. (2009). The antiproliferative effect of EPA in HL60 cells is mediated by alterations in calcium homeostasis. Lipids, 44(2), 103-113. doi: 10.1007/s11745-008-3263-5
Song, K. S., Jing, K., Kim, J. S., Yun, E. J., Shin, S., Seo, K. S., . . . Lim, K. (2011). Omega-3-polyunsaturated fatty acids suppress pancreatic cancer cell growth in vitro and in vivo via downregulation of Wnt/Beta-catenin signaling. Pancreatology, 11(6), 574-584. doi: 10.1159/000334468
Takatori, H., Natsugoe, S., Okumura, H., Matsumoto, M., Uchikado, Y., Setoyama, T., . . . Aikou, T. (2008). Cyclooxygenase-2 expression is related to prognosis in patients with esophageal squamous cell carcinoma. Eur J Surg Oncol, 34(4), 397-402. doi: 10.1016/j.ejso.2007.04.011
Zhang, S., Zhang, X. Q., Ding, X. W., Yang, R. K., Huang, S. L., Kastelein, F., . . . Zou, X. P. (2014). Cyclooxygenase inhibitors use is associated with reduced risk of esophageal adenocarcinoma in patients with Barrett's esophagus: a meta-analysis. Br J Cancer, 110(9), 2378-2388. doi: 10.1038/bjc.2014.127