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Evidence indicates that COX2\/PGE2\/EP axis has a critical role in tumorogenesis and chemoresistance. This study assessed the relation of the COX-2 gene expression with chemoresistance in colon cancer (CC) patients. Also, it explored the effect of chemotherapy on COX-2 expression. The study included 24 patients with CC without chemotherapeutic treatment and 24 chemoresistant CC patients. Tumor and adjacent non-neoplastic colon tissue samples were collected and COX-2 mRNA expression was measured. Also, COX-2 and its related genes; TROP2 and DUSP4 expression were analysed in 5 flurouracil and Oxalliplatin treated Caco-2 and SW-620 cells. The results indicated significant upregulation of COX-2 expression in tissues of chemoresistant CC patients when compared with that in CC tissues without chemotherapy (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). There was a relation between COX-2 expression with lymph nodes, metastases and staging in both groups. Concerning in-vitro experiments, there was a dose dependent significant increase of COX-2, TROP2 and DUSP4 mRNA and protein expression levels in 5flurouracil and Oxalliplatin treated cells. These findings demonstrated that overexpression of COX-2 in the chemoresistant CC patients. Both 5 flurouracil and Oxalliplatin induced COX-2 overexpression and in turn COX-2 upregulation may decrease the response of cancer to chemotherapy.<\/jats:p>","DOI":"10.1038\/s41598-025-98451-9","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T15:28:37Z","timestamp":1746545317000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The interplay between COX-2, chemotherapeutic drugs, and chemoresistance in colon cancer"],"prefix":"10.1038","volume":"15","author":[{"given":"Sally M.","family":"Shalaby","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma A.","family":"Shawky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Ashour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walaa","family":"Sarhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"issue":"2","key":"98451_CR1","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1136\/gutjnl-2022-327736","volume":"72","author":"E Morgan","year":"2023","unstructured":"Morgan, E. et al. 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