槐耳通过改善肠道菌群增强奥沙利铂对胃癌的疗效OA
Huaier Enhances Efficacy of Oxaliplatin in Treatment of Gastric Cancer by Improving Gut Microbiota
目的 阐明槐耳增强奥沙利铂(OXA)抗胃癌(GC)疗效过程中,肠道菌群变化及其分子机制.方法 通过16S rRNA测序、RT-qPCR及IHC分析槐耳对MKN45荷瘤小鼠肠道菌群结构及肠道屏障功能的影响;采用超高效液相色谱—串联质谱法(UPLC-MS)、网络药理学方法,结合体内实验,系统探究槐耳中的关键活性成分,并阐明其发挥抗GC治疗作用的潜在机制;Western blot实验检测癌细胞及癌组织中PI3K/AKT/SREBP通路的表达水平;通过血清生化指标检测及HE染色组织切片分析,验证槐耳与OXA联合用药的安全性.结果 槐耳通过提高嗜黏蛋白阿克曼菌(A.muciniphila)的丰度,抑制PI3K/AKT/SREBP通路,减少脂滴沉积,最终提高GC治疗中肿瘤细胞对OXA的敏感性.结论 本研究明确了槐耳作为GC治疗药物提高化疗敏感性的应用价值,并从分子机制及肠道菌群角度为槐耳发挥系统性治疗作用提供了新思路.
Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin(OXA)chemotherapy in gastric cancer(GC).Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing,RT-qPCR,and IHC.UPLC-MS and network pharmacology,as well as in vivo experimental approaches,were employed to investigate the key bioactive constituents of huaier systema-tically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC.The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis.The safety profile of huaier combined with OXA was verified through serum bioche-mistry and HE-stained tissue section analyses.Results Hua-ier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila,reduced lipid droplet deposition,and ultimately enhanced the sensitivity to OXA in the treatment of GC.Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.
张胜莲;王瑞智;高玉亭;张桓虎;石新丽;杜智敏;龚艺;兰美琦;刘萍;熊亚军;公艳丽;宋晓永;李俊丽
030000 太原,山西中医药大学中西医结合肿瘤免疫研究室030001 太原,山西省肿瘤医院肝胆胰胃外科030000 太原,山西中医药大学中西医结合肿瘤免疫研究室030001 太原,山西省肿瘤医院肝胆胰胃外科||030013 太原,山西医科大学附属肿瘤医院中西医结合内科030000 太原,山西中医药大学中西医结合肿瘤免疫研究室030000 太原,山西中医药大学中西医结合肿瘤免疫研究室030000 太原,山西中医药大学中西医结合肿瘤免疫研究室030000 太原,山西中医药大学中西医结合肿瘤免疫研究室030000 太原,山西中医药大学中西医结合肿瘤免疫研究室030000 太原,山西中医药大学中西医结合肿瘤免疫研究室030000 太原,山西中医药大学中西医结合肿瘤免疫研究室030000 太原,山西中医药大学中西医结合肿瘤免疫研究室030000 太原,山西中医药大学中西医结合肿瘤免疫研究室
医药卫生
槐耳胃癌PI3K/AKT/SREBP通路肠道菌群肠道屏障
HuaierGastric cancerPI3K/AKT/SREBP path-wayGut microbiotaIntestinal barrier
《肿瘤防治研究》 2026 (3)
176-186,11
国家自然科学基金(82072740)山西省基础研究计划(202403021221199)山西中医药大学高层次引进人才科研启动基金(2023RC03) The National Natural Science Foundation of China(No.82072740)The Fundamental Research Program of Shan-xi Province(No.202403021221199)The Foundation for High-level Talents of Shanxi University of Chinese Medicine(No.2023RC03)
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