Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
Department of Oncology, The First Affiliated Hospital of Fujian Medical University Fuzhou, China.
Exp Cell Res. 2020 Apr 1;389(1):111856. doi: 10.1016/j.yexcr.2020.111856. Epub 2020 Jan 22.
CES-2 (carboxylesterase-2) belongs to the carboxylesterase gene family, which plays crucial roles in lipid mobilization and chemosensitivity to irinotecan. However, its role in chemosensitivity to oxaliplatin (L-OHP) remains unclear. Herein, L-OHP-resistant cells (HCT-116L and RKOL) were established by increasing the concentration of L-OHP. The results showed that CES2 expression was upregulated in L-OHP-resistant tissues and cells lines (both P < 0.01). Low expression of CES2 correlated with a better survival, and the results were further confirmed in the R2 platform: a biologist friendly web-based genomics analysis and visualization application. Downregulation of CES2 suppressed cell proliferation, induced apoptosis and reversed L-OHP resistance by medicating the PI3K signaling pathway in L-OHP-resistant cells. However, both PI3K inhibitor (LY294002) and activator (IGF-1) could not medicate CES2 expression. These findings indicated that CES2 may be utilized as a novel biomarker and therapeutic target for L-OHP resistance in CRC treatment.
CES-2（羧酸酯酶-2）属于羧酸酯酶基因家族，在脂质动员和对伊立替康的化疗敏感性中起着关键作用。然而，其在奥沙利铂（L-OHP）化疗敏感性中的作用尚不清楚。本研究通过增加 L-OHP 的浓度建立了 L-OHP 耐药细胞（HCT-116L 和 RKOL）。结果表明，CES2 在 L-OHP 耐药组织和细胞系中表达上调（均 P<0.01）。CES2 的低表达与较好的生存相关，这一结果在 R2 平台上得到了进一步证实：一个生物友好型基于网络的基因组学分析和可视化应用。下调 CES2 通过调节 PI3K 信号通路抑制 L-OHP 耐药细胞的增殖，诱导细胞凋亡，并逆转 L-OHP 耐药性。然而，PI3K 抑制剂（LY294002）和激活剂（IGF-1）均不能调节 CES2 的表达。这些发现表明，CES2 可能作为 CRC 治疗中 L-OHP 耐药的新型生物标志物和治疗靶点。
