Xu Wanjun, Wang Jianjun, Han Wencan, Sun Jinmin, Yang Xuemei, Li Xiaomin, Pei Dongsheng
Department of Pathology, Laboratory of Clinical and Experimental Pathology, National Demonstration Center for Experimental Basic Medical Science Education, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Department of Histology and Embryology, Wannan Medical College, Wuhu, 241002, Anhui, China.
Med Oncol. 2025 Jun 13;42(7):257. doi: 10.1007/s12032-025-02801-6.
The efficacy of 5-fluorouracil treatment for colorectal cancer (CRC) is substantially compromised by drug resistance, although the underlying mechanisms remain unclear. In this research, we aimed to explore the role and mechanism of action of CXC motif chemokine ligand 5 (CXCL5) in 5-fluorouracil resistance. RNA sequencing was conducted to detect abnormally expressed genes in the 5-fluorouracil-resistant colon cancer cell line, HCT8-5FU. CXCL5 expression in CRC tissues and cell lines was evaluated using RT-qPCR, western blotting, and immunohistochemistry. In vivo and in vitro assays were conducted to evaluate the role of CXCL5 in the promotion of CRC progression. Mass spectrometry and co-immunoprecipitation were employed to investigate the role of CXCL5 in CRC development and 5-fluorouracil resistance. Immunofluorescence and western blot analyses were employed to determine the subcellular localization of CXCL5 and its associated signaling pathways. CXCL5 expression was elevated in both CRC tissues and cell lines. CXCL5 promoted CRC cell growth and resistance to 5-fluorouracil in both in vitro and in vivo settings. Mechanistically, CXCL5 may modulate the MDM2/p53 axis to inhibit p21 by binding to RALY. In this study, CXCL5 accelerated CRC progression and increased CRC cell resistance to 5-fluorouracil via the inhibition of p21 expression. Thus, CXCL5 is a potential target for CRC therapeutic strategies.
尽管潜在机制尚不清楚，但5-氟尿嘧啶治疗结直肠癌（CRC）的疗效因耐药性而大打折扣。在本研究中，我们旨在探讨CXC基序趋化因子配体5（CXCL5）在5-氟尿嘧啶耐药中的作用及作用机制。进行RNA测序以检测5-氟尿嘧啶耐药结肠癌细胞系HCT8-5FU中异常表达的基因。使用RT-qPCR、蛋白质免疫印迹和免疫组织化学评估CXCL5在CRC组织和细胞系中的表达。进行体内和体外实验以评估CXCL5在促进CRC进展中的作用。采用质谱分析和免疫共沉淀研究CXCL5在CRC发展和5-氟尿嘧啶耐药中的作用。采用免疫荧光和蛋白质免疫印迹分析确定CXCL5的亚细胞定位及其相关信号通路。CXCL5在CRC组织和细胞系中均表达升高。在体外和体内环境中，CXCL5均促进CRC细胞生长并增强其对5-氟尿嘧啶的耐药性。机制上，CXCL5可能通过与RALY结合来调节MDM2/p53轴以抑制p21。在本研究中，CXCL5通过抑制p21表达加速CRC进展并增加CRC细胞对5-氟尿嘧啶的耐药性。因此，CXCL5是CRC治疗策略的一个潜在靶点。
