桂枝茯苓丸干预卵巢癌干细胞特性的作用及机制研究  

Interventions of Guizhi Fuling Pills in Properties of Ovarian Cancer Stem Cells

作　　者：卜子轩 薛梦微 田佳微 柯凯乐 王紫颖 李潇[2] 卢天公 BU Zixuan;XUE Mengwei;TIAN Jiawei;KE Kaile;WANG Ziying;LI Xiao;LU Tiangong(School of Life Sciences,Beijing University of Chinese Medicine,Beijing 102488,China;Department of Haemato-Oncology,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学生命科学学院,北京102488 [2]北京中医药大学东直门医院血液肿瘤科,北京102488

出　　处：《中国药物警戒》2025年第3期263-270,共8页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(82104460):桂枝茯苓丸在抑制卵巢癌中与STAT3相关的分子调控机制解析;北京中医药大学揭榜挂帅项目(2022-JYB-JBZR-023):桂枝茯苓丸抑制妇科肿瘤的药效机制研究及临床分子验证;北京中医药大学校级高层次人才项目(2021-XJ-KYQD-009):中药预防恶性肿瘤发生技术构建及应用。

摘　　要：目的探讨桂枝茯苓丸干预卵巢癌干细胞特性的潜在药理作用。方法利用UPLC-MS解析桂枝茯苓丸活性成分;通过网络药理学预测其干预卵巢癌干性的潜在作用靶点和通路;体外成球实验观察对卵巢癌细胞成球能力;免疫荧光观察给药后细胞中p-STAT3的表达;qRT-PCR和蛋白免疫印迹法分别检测细胞中干性标志物mRNA和蛋白的表达水平。结果得到桂枝茯苓丸活性成分95个,与卵巢癌干性相关靶点350个,桂枝茯苓丸可能通过调节PI3K/AKT1、STAT3等信号通路干预卵巢癌干性发展。药理学研究发现,该方抑制卵巢癌成球能力,干预STAT3活化及核内表达,调控干性基因CD44、ALDH1的表达。结论桂枝茯苓丸对卵巢癌干性的抑制性表现出多靶点多通路特点,其抑制干性标志物ALDH1和CD44的机制与STAT3密切相关。Objective To investigate the potential pharmacology of Guizhi Fuling pills in intervening in stem cells of ovarian cancer.Methods UPLC-MS was adopted to analyze the active ingredients of Guizhi Fuling pills while network pharmacology was used to predict the potential targets and pathways through which Guizhi Fuling pills might intervene in ovarian cancer stemness.In vitro sphere formation assay was performed to observe the sphere-forming ability of ovarian cancer cells.Immunofluorescence was used to detect the expression of p-STAT3 in cells.qRT-PCR and protein immunoblotting were performed to detect the mRNA and protein levels of stemness markers,respectively.Results Ninetyfive active ingredients and 350 targets were obtained from Guizhi Fuling pills that might intervene in the stemness of ovarian cancer by regulating such signaling pathways as PI3K/AKT1 and STAT3.Pharmacological studies showed that Guizhi Fuling pills inhibited the spheroid formation of ovarian cancer cells,intervened in STAT3 activation and nuclear expression,and regulated the expressions of stemness genes CD44 and ALDH1 family.Conclusion Guizhi Fuling pills suppress ovarian cancer stemness through multi-targets and multi-pathways.The mechanism by which Guizhi Fuling pills inhibits stemness markers ALDH1 and CD44 is closely related to STAT3.

关 键 词：桂枝茯苓丸 卵巢癌 肿瘤干细胞 网络药理学 作用机制 

分 类 号：R979.1[医药卫生—药品] R994.11[医药卫生—药学]