蜚蠊改善错配修复基因缺失肠癌细胞对氟尿嘧啶敏感性的机制研究  

Study with cockroach improves fluorouracil sensitivity in dMMR colorectal cancer

作　　者：彭雯[1] 秦琴 王巧 谭诗生[1] PENG wen;QIN Qin;WANG Qiao(Department of Oncology,The People's Hospital of Guizhou Province,Guiyang(550002),China)

机构地区：[1]贵州省人民医院,贵州贵阳550002 [2]龙里县人民医院,贵州贵阳522730

出　　处：《中国中西医结合外科杂志》2024年第1期119-123,共5页Chinese Journal of Surgery of Integrated Traditional and Western Medicine

基　　金：贵州省中医药管理局中医药、民族医药科学技术研究课题(QZYY-2021-014);贵州省科技计划项目(黔科合基础〔2020〕1Y339);贵州省卫生健康委科学技术基金项目(gzwkj 2023-011)。

摘　　要：目的:探讨中药蜚蠊改善氟尿嘧啶对错配修复基因缺失(dMMR)肠癌细胞敏感性的相关机制。方法:选择dMMR肠癌细胞,予以不同浓度氟尿嘧啶和蜚蠊作用后,利用MTT法检测两药联合的抑瘤性,根据抑制率计算出治疗指数(CI)值,明确联合增效作用,应用二代基因测序及脂质代谢分析,挖掘出差异代谢基因,数据库分析差异基因与相关机制通路。结果:中药蜚蠊可以改善氟尿嘧啶在HCT116和DLD1肠癌细胞中的疗效,GO功能富集分析和KEGG分析结果显示脂质代谢、自噬调控和凋亡通路发生主要改变,利用LC/MS进行脂质组学检测,共有153个脂质分子发生变化,包括脂肪类、鞘脂代谢物、磷脂代谢物和甘油酯。结论:蜚蠊与氟尿嘧啶联合用于dMMR肠癌细胞具有协同增效作用,可能通过调控代谢通路、自噬及凋亡通路机制改善药物疗效。Objective To explore the mechanisms by which the Chinese medicine Cockroach improves the sensitivity of fluorouracil to dMMR colorectal cancer cells.Methods After selecting the mismatch repair gene-deficient colorectal cancer cells.The combined anti-tumor effects of these two drugs were assessed using the MTT method.The combination index was calculated based on the inhibition rate to determine the synergistic effect.The second-generation gene sequencing and lipid metabolism analysis were employed to identify differential metabolic genes,and database analysis was conducted to understand the pathways associated with differential genes.Results The cockroach was found to enhance the efficacy of 5-FU in HCT116 and DLD1 cells.GO functional enrichment analysis and KEGG analysis showed significant alterations in lipid metabolism,autophagy regulation,and apoptosis pathways.Further lipidomics analysis using LC/MS revealed statistically significant changes in a total of 153 lipid molecules,including lipids,sphingolipid metabolites,phospholipid metabolites,and glycerides.Conclusion The combination of cockroach and 5-FU demonstrates a synergistic enhancement of efficacy against dMMR colorectal cancer cells.This effect is likely achieved by modulating metabolic pathways,autophagy,and apoptosis mechanisms.It provides a theoretical basis for the clinical use of fluorouracil in the treatment of dMMR colorectal cancer patients.

关 键 词：大肠癌 错配修复基因 氟尿嘧啶 蜚蠊 脂质代谢 

分 类 号：R735.34[医药卫生—肿瘤]