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
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: 15 dec. 2024.
Keywords
cyclooxygenase-2, eicosapentaenoic acid, esophageal squamous cell carcinoma, immunohistochemistry, prognosis
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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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
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