Shalaby Sally M, Shawky Salma A, Ashour Hassan, Sarhan Walaa
Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Surgery Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Sci Rep. 2025 May 6;15(1):15837. doi: 10.1038/s41598-025-98451-9.
Chemoresistance and tumor relapse remain major clinical problems. 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 (p < 0.001). 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.
化疗耐药和肿瘤复发仍然是主要的临床问题。有证据表明，COX2/PGE2/EP轴在肿瘤发生和化疗耐药中起关键作用。本研究评估了COX-2基因表达与结肠癌（CC）患者化疗耐药之间的关系。此外，还探讨了化疗对COX-2表达的影响。该研究纳入了24例未经化疗的CC患者和24例化疗耐药的CC患者。收集肿瘤及相邻的非肿瘤性结肠组织样本，检测COX-2 mRNA表达。此外，还分析了在5-氟尿嘧啶和奥沙利铂处理的Caco-2和SW-620细胞中COX-2及其相关基因TROP2和DUSP4的表达。结果表明，与未化疗的CC组织相比，化疗耐药CC患者组织中COX-2表达显著上调（p < 0.001）。两组中COX-2表达与淋巴结、转移和分期之间均存在关联。关于体外实验，在5-氟尿嘧啶和奥沙利铂处理的细胞中，COX-2、TROP2和DUSP4的mRNA和蛋白表达水平呈剂量依赖性显著增加。这些发现表明化疗耐药的CC患者中COX-2过表达。5-氟尿嘧啶和奥沙利铂均诱导COX-2过表达，反过来COX-2上调可能会降低癌症对化疗的反应。
