肿瘤预防与治疗2025，Vol.38Issue(8)：661-670,10.DOI:10.3969/j.issn.1674-0904.2025.08.001
桂枝茯苓方通过调控TNF-α/NF-κB信号通路发挥抗卵巢透明细胞癌的作用
Guizhi Fuling Formula Suppresses Ovarian Clear Cell Carcinoma by Reg-ulating the TNF-α/NF-κB Signaling Pathway
摘要
Abstract
Objective:To explore the therapeutic effects and underlying mechanisms of Guizhi Fuling Formula against ovarian clear cell carcinoma through in vivo and in vitro experi-ments,validated by network pharmacology analysis.Methods:MTT assay was performed to assess the inhibitory effects of Guizhi Fuling Formula on proliferation of ovarian clear cell carcinoma cells.ES-2 cells were used to establish xenograft mod-els of ovarian clear cell carcinoma in nude mice.Mice bearing ES-2 tumors were treated with gradient doses of Guizhi Fuling Formula extract,and tumor volume was monitored to calculate the inhibitory rate.RNA-seq was performed to profile differen-tially expressed genes following Guizhi Fuling Formula extract treatment.Enrichment analyses of GO,KEGG,and GSEA were then conducted to delineate the signaling pathways modulated by these genes.The RNA-seq findings were corroborated by net-work pharmacology analysis.Results:Guizhi Fuling Formula extract inhibited ovarian cancer cell proliferation in a concentra-tion-and time-dependent manner.ES-2 ovarian clear cell carcinoma cells exhibited greater sensitivity to this extract than oth-er ovarian cancer cell lines.Compared with the control group,high-dose Guizhi Fuling Formula extract(20.0 g/kg)signifi-cantly suppressed tumor growth in ES-2 xenograft-bearing nude mice(P=0.041),achieving a tumor growth inhibition rate of 52.7%.Furthermore,no observable toxicity was detected in treated mice.Transcriptomic RNA-seq analysis revealed that treatment with Guizhi Fuling Formula extract induced differential changes in 75 regulatory genes.GO and KEGG enrichment analyses demonstrated that the extract modulates biological processes including cell cycle arrest,cell development,and growth,along with multiple signaling pathways such as cancer pathways,IL-17 signaling pathway,Toll-like receptor signa-ling,and FOXO signaling.GSEA and network pharmacology analyses revealed that inhibition of the TNF-α/NF-κB signaling pathway is one of the important mechanisms underlying Guizhi Fuling formula extract's efficacy against ovarian clear cell car-cinoma.Conclusion:Guizhi Fuling Formula exerts anti-tumor effects against ovarian clear cell carcinoma through multiple mechanisms,with inhibition of the TNF-α/NF-κB signaling pathway being a principal one.关键词
卵巢透明细胞癌/桂枝茯苓方/网络药理学/TNF-α/NF-κB信号通路/抗肿瘤作用Key words
Ovarian clear cell carcinoma/Guizhi Fuling Formula/Network pharmacology/TNF-α/NF-κB signaling path-way/Anti-tumor effect分类
医药卫生引用本文复制引用
朱世瑞,唐晴,许玉珉,雷辉,施丽红..桂枝茯苓方通过调控TNF-α/NF-κB信号通路发挥抗卵巢透明细胞癌的作用[J].肿瘤预防与治疗,2025,38(8):661-670,10.基金项目
This study was supported by grants from Health Commission of Henan Province(No.Yu Wei Zhong Yi Han[2021]16). 河南省第二批中医药青苗人才培养项目(编号:豫卫中医函[2021]16号) （No.Yu Wei Zhong Yi Han[2021]16）
