白藜芦醇靶向FLG抑制甲状腺癌细胞增殖、侵袭及迁移  

Resveratrol targets FLG to inhibit thyroid cancer cells'proliferation,invasion and migration

作　　者：刘诗韵 刘仁炎 明庭文 刘经健 王珊[2] 杨洋 陈琴华 朱军 LIU Shiyun;LIU Renyan;MING Tingwen;LIU Jingjian;WANG Shan;YANG Yang;CHEN Qinhua;ZHU Jun(School of Pharmaceutical Science,Hubei University of Medicine,Hubei Shiyan 442000,China;Department of Pharmacy,Dongfeng General Hospital of Traditional Chinese Medicine,Hubei Shiyan 442008,China;Hubei Key Laboratory of Wudang Local Chinese Medicine Research,Hubei Shiyan 442002,China;Key Laboratory of TCM Clinical Pharmacy,Shenzhen Baoan Authentic TCM Therapy Hospital,Guangdong Shenzhen 518101,China)

机构地区：[1]湖北医药学院药学院,湖北十堰442000 [2]湖北医药学院附属国药东风总医院药学部,湖北十堰442008 [3]武当特色中药研究湖北省重点实验室,湖北十堰442002 [4]深圳市宝安纯中医治疗医院中药临床药学重点实验室,广东深圳518101

出　　处：《中国医院药学杂志》2024年第22期2606-2611,2627,共7页Chinese Journal of Hospital Pharmacy

基　　金：十堰市科技局项目(编号:22Y90);深圳市‘医疗卫生三名工程’项目(编号:SZZYSM202106004);中国医药教育协会“聚火优才”全国药学服务科研项目(编号:CMEAPC2023029)。

摘　　要：目的:探讨白藜芦醇(resveratrol,Res)对甲状腺癌细胞的作用,分析作用靶点及信号通路。方法:CCK-8法检测Res对甲状腺癌细胞TPC-1、FTC-133、BC-PAP存活率的影响,选择对Res耐受度最低的TPC-1细胞进行克隆试验、划痕试验、Transwell试验,检测Res对细胞增殖、迁移、侵袭能力的影响。mRNA-seq筛选Res调控的差异基因(differential genes,DEGs),对DEGs进行GO&KEGG分析,qRT-PCR验证DEGs,Western blot检测p53信号通路相关蛋白变化。KaplanMeier plotter分析DEGs与甲状腺癌患者总生存期的关联,敲低基因FLG的表达并验证敲低效率,CCK-8法、克隆试验、划痕试验、Transwell试验检测FLG敲低后细胞增殖、侵袭、迁移能力变化。结果:Res显著抑制TPC-1、FTC-133、BC-PAP的细胞存活率,抑制TPC-1细胞增殖、侵袭、迁移能力。p53信号通路是Res作用的关键信号通路,Res上调p53蛋白表达,下调蛋白p21表达。FLG敲低后细胞增殖、侵袭及迁移能力下降。结论:FLG可能促进甲状腺癌的发展。Res显著抑制甲状腺癌细胞增殖、侵袭及迁移能力,其机制可能与抑制FLG和p53信号通路表达有关。OBJECTIVE To explore the effect of resveratrol(Res)on thyroid cancer cells and analyze the target spot and sig-naling pathways.METHODS CCK-8 method was utilized for detecting the effect of Res on survival rate of thyroid cancer cells TPC-1,FTC-133 and BC-PAP.TPC-1 cells with the lowest tolerance to Res were selected for cloning,scratch and Transwell experiments to detect the effect of Res on cell proliferation,migration and invasion.mRNA-seq screened Res regulated differen-tial genes(DEGs)and GO&KEGG analysis was performed on DEGs.Quantitative real-time polymerase chain reaction(qRT-PCR)was utilized for verifying DEGs and Western blot for detecting the changes of p53 signaling pathway-related proteins.Kaplan-Meier database was employed for examining the association between DEGs and overall survival(OS)of thyroid cancer patients.The expression of FLG in knockdown genes was verified and knockdown efficiency examined.CCK-8 method,cloning,scratch and Transwell assays were utilized for detecting the changes in cell proliferation,invasion and migration after FLG knock-down.RESULTS Res arrested the survival rate of TPC-1,FTC-133 and BC-PAP cells and stunted the proliferation,invasion and migration of TPC-1 cells.p53 signaling pathway is a key signaling pathway.Res up-regulated p53 protein expression and down-regulated p21 expression.Cell proliferation,invasion and migration declined after FLG knockdown.CONCLUSION FLG may promote the development of thyroid cancer.Res significantly suppresses the proliferation,invasion and migration of thy-roid cancer cells.Its mechanism may be related to an inhibition of FLG and p53 signaling pathways.

关 键 词：mRNA-seq分析 白藜芦醇 甲状腺癌 FLG p53信号通路 

分 类 号：R966[医药卫生—药理学]