具核梭杆菌通过其毒力因子LPS激活TLR4/MYD88/NF-κB通路促进食管鳞癌增殖  

Fusobacterium nucleatum in activating the TLR4/MYD88/NF-κB pathway through its virulence factor LPS to promote the proliferation of esophageal squamous cell carcinoma

作　　者：唐帅 张桂生 黄杨文 朱慎钰[4] 曾雪亮[5] 何新[2,3] TANG Shuai;ZHANG Gui-sheng;HUANG Yang-wen;ZHU Shen-yu;ZENG Xue-liang;HE Xin(Department 3 of Internal Medicine,Longnan Branch of The First Affiliated Hospital of Gannan Medical University;Department of Respiratory and Critical Care Medicine,The First Affiliated Hospital of Gannan Medical University;Jiangxi Provincial Branch of National Clinical Research Center for Geriatric Diseases;Department of Thoracic Surgery,The First Affiliated Hospital of Gannan Medical University;Department of Pharmacy,The First Affiliated Hospital of Gannan Medical University,Ganzhou,Jiangxi 341000)

机构地区：[1]赣南医学院第一附属医院龙南分院内3科 [2]赣南医学院第一附属医院呼吸与危重症医学科 [3]国家老年疾病临床医学研究中心江西省分中心 [4]赣南医学院第一附属医院胸外科 [5]赣南医学院第一附属医院药剂科,江西赣州341000

出　　处：《赣南医学院学报》2022年第6期569-575,共7页JOURNAL OF GANNAN MEDICAL UNIVERSITY

基　　金：江西省自然科学基金项目(20202BABL216055);江西省教育厅基金项目(GJJ190792)。

摘　　要：目的:探讨具核梭杆菌通过其毒力因子LPS激活TLR4/MYD88/NF-κB通路促进食管鳞癌增殖的分子机制。方法:16S rRNA基因测序分析25例食管癌患者及25例正常对照组的细菌群落组成;通过MTT实验和集落形成试验,并联合TLR4通路抑制剂,检测具核梭杆菌对人食管鳞癌细胞系TE-1和EC18增殖的影响;Western Blot实验检测具核梭杆菌刺激TE-1和EC18细胞后TLR4/MYD88/NF-κB通路及增殖相关蛋白的表达水平。结果:具核梭杆菌在食管鳞癌患者肿瘤组织中明显富集。加入具核梭杆菌感染食管鳞癌细胞(TE-1和EC18)后,食管鳞癌细胞增殖能力增强。加入具核梭杆菌的LPS也可以促进食管鳞癌细胞的增殖。具核梭杆菌可以上调TLR4/MYD88/NF-κB通路相关蛋白的表达。结论:具核梭杆菌在食管鳞癌发生、发展过程中起重要作用,其可能通过毒力因子LPS激活TLR4/MYD88/NF-κB通路促进食管鳞癌细胞增殖。Objective:To investigate the molecular mechanism of Fusobacterium nucleatum(F.nucleatum)in activating TLR4/MYD88/NF-κB pathway through its virulence factor LPS to promote the proliferation of esophageal squamous cell carcinoma.Methods:16S rRNA gene sequencing was used to analyze the bacterial community composition of 25 patients with esophageal cancer and 25 normal controls;through MTT experiment and colony formation test,combined with TLR4pathway inhibitors,the effect of F.nucleatum on human esophageal squamous cell carcinoma TE-1 and the effect of EC18 proliferation;Western Blot experiment was used to detect the expression levels of TLR4/MYD88/NF-κB pathway and proliferation-related proteins after F.nucleatum stimulated TE-1 and EC18 cells.Results:F.nucleatumwas significantly enriched in tumor tissues of ESCC patients.When F.nucleatum was added to infect esophageal squamous cell carcinoma cells(TE-1 and ec18),the proliferation of esophageal squamous cell carcinoma cells was enhanced.At the same time,LPS added with F.nucleatum could also promote the proliferation of esophageal squamous cell carcinoma cells.It was also found that F.nucleatum could upregulate the expression of proteins related to TLR4/MYD88/NF-κB pathway.Conclusion:F.nucleatumplays an important role in the occurrence and development of esophageal squamous cell carcinoma.It may activate TLR4/MYD88/NF-κB pathway through its virulence factor LPS to promote the proliferation of esophageal squamous cell carcinoma.

关 键 词：具核梭杆菌 食管鳞癌 增殖 

分 类 号：R735.1[医药卫生—肿瘤] R378.8[医药卫生—临床医学]