雷公藤红素促进癌旁脂肪细胞分泌脂联素抗肾透明细胞癌上皮间充质转化作用  

Celastrol promotes the secretion of adiponectin by adjacent adipocytes and inhibits the EMT of renal clear cell carcinoma

作　　者：何鹏 张婵娟 石雅宁 朱能[4] 陈聪 彭柳 覃丽 HE Peng;ZHANG Chan-juan;SHI Ya-ning;ZHU Neng;CHEN Cong;PENG Liu;QIN Li(Laboratory of Stem Cell Regulation and Application of Traditional Chinese Medicine,School of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208;Department of Pharmacy,School of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208;Science and Technology Innovation Center,Hunan University of Chinese Medicine,Changsha 410208;The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007;Hunan Key Laboratory of Vascular Biology and Translational Medicine,Hunan University of Chinese Medicine,Changsha 410208)

机构地区：[1]湖南中医药大学药学院干细胞中药调控与应用实验室,长沙410208 [2]湖南中医药大学药学院药剂学教研室,长沙410208 [3]湖南中医药大学科技创新中心,长沙410208 [4]湖南中医药大学第一附属医院,长沙410007 [5]湖南中医药大学血管生物学与转化医学湖南省重点实验室,长沙410208

出　　处：《中南药学》2025年第3期638-643,共6页Central South Pharmacy

基　　金：湖南省自然科学基金科药联合基金(No.2022JJ80088);国家自然科学基金项目(No.82274159);湖南省卫生健康委员会重点指导课题(No.202213055529);湖南省自然科学基金青年项目(No.2023JJ40485);湖南省教育厅优秀青年项目(No.22B0355)。

摘　　要：目的探讨雷公藤红素(CeT)诱导癌旁脂肪细胞分泌脂联素(APN)抑制人肾透明细胞癌细胞株786-O增殖迁移的作用机制。方法通过CCK 8法检测CeT对786-O和3T3-L1细胞的毒性,诱导3T3-L1分化并采用油红O染色检测3T3-L1细胞分化情况,通过ELISA检测不同浓度CeT对于3T3-L1细胞分化后的成熟脂肪细胞分泌脂联素情况。建立786-O和3T3-L1细胞共培养体系,采用划痕实验、EDU检测共培养体系对786-O细胞增殖、迁移能力的影响,并采用Western blot法检测上皮间充质转化(EMT)相关蛋白(E-cad、N-cad、Snail、Vim)、Adiponectin等相关蛋白的表达。结果50、100、200 nmol·L^(-1)的CeT可刺激成熟脂肪细胞分泌脂联素,抑制肾癌细胞增殖和迁移;共培养后786-O细胞中EMT相关蛋白N-cad、Snail、Vim的表达水平显著下调,E-cad表达水平上升。结论CeT通过诱导脂肪细胞分泌脂联素抑制肾透明细胞癌EMT进程。Objective To determine the mechanism by which celastrol induces the secretion of adiponectin by adjacent adipocytes to inhibit the invasion and metastasis of cell line 786-O in human renal clear cell carcinoma.Methods The toxicity of celasterol on 786-O and 3T3-L1 cells was detected with CCK 8 assay.ELISA was used to test the secretion of adiponectin by mature adipocytes differentiated from 3T3-L1 cells at different concentrations of celastrol.Oil red O staining was used to measure the differentiation of 3T3-L1 cells.The co-culture system for 786-O and 3T3-L1 cells was successfully established.Wound healing and EDU assays were used to examine the effect of the co-culture system on the migration and proliferation of 786-O cells.Western blot was used to detect the expression of epithelial-mesenchymal transition(EMT)related proteins such as E-cadherin,N-cadherin,Snail,Vimentin,Adiponectin and so on.Results Celastrol stimulated mature adipocytes to secrete adiponectin at 50,100,and 200 nmol·L^(-1),inhibited the proliferation and migration of renal cancer cells.The expressions of N-cadherin,Snail,and Vimentin in 786-O cells were substantially down-regulated after the co-culture,while the expression level of E-cadherin was increased.Conclusion Celastrol can inhibit the EMT progression of renal clear cell carcinoma by inducing adiponectin secretion of adipocytes.

关 键 词：雷公藤红素 肾透明细胞癌 脂联素 共培养 

分 类 号：R286[医药卫生—中药学]