Volume 4,Issue 9
六味地黄丸/RXRa/PI3K-AKT 轴向调控前列腺癌的作用机制
六味地黄丸(LWDHP)在临床实践中展现出对抗前列腺癌的潜在疗效,然而其背后的作用机制仍未阐明。本研究整合网络药理预测、生物信息分析及实验验证,旨在揭示该方剂发挥抗癌功效的分子基础。通过筛选LWDHP 所含活性组分,获取药物靶点与疾病相关靶标的交集;实施网络拓扑结构解析与功能富集评估;并借助蛋白质印迹法检测关键蛋白的表达水平。最终鉴定出69种具有生物活性的化学实体,以及186个核心作用基因;其中槲皮素被确认为主要活性成分,重要靶点涵盖RXRa、PTGS2与HSP90AA1;核心基因富集于PI3K-Akt 和TNF 通路。实验证实,LWDHP 下调前列腺癌细胞RXRa 表达并改变AKT 磷酸化水平。LWDHP 通过“多成分- 多靶点- 多通路”协同模式,尤其调节RXRa 介导的PI3K-Akt 信号轴,发挥抗前列腺癌效应。
[1]LIF,YUY,JIANGM,etal.Targetsforimprovingprostatetumorresponsetoradiotherapy[J].EuropeanJournalofPharmacology,2025,986:177149.
[2]TSAIJ-J,YENC-Y,HSUC-H,etal.ImmunomodulatoryeffectsofmodifiedLiu-Wei-Di-Huang-WantraditionalChinesemedicineonallergicasthmaticmice[J].Allergy,Asthma&Clin
icalImmunology,2023,19(1):35.
[3]LIS,CHENJ,HUY,etal.networkpharmacologyandAI[J].JEthnopharmacol,2023,307:116260.
[4]WUZ,YUX,ZHANGS,etal.TheroleofPI3K/AKTsignalingpathwayingallbladdercarcinoma[J].AmericanJournalofTranslationalResearch,2022,14(7):4426.
[5]YEY,LIUM,WUF,etal.TRMT6promoteshepatocellularcarcinomaprogressionthroughthePI3K/AKTsignalingpathway[J].EuropeanJournalofMedicalResearch,2023,28(1):48.
[6]ZHANX,LIH,JINJ,etal.NetworkpharmacologyandexperimentalvalidationtoexploretheroleandpotentialmechanismofLiuweiDihuangDecoctioninprostatecancer[J].BMCcomplem
entarymedicineandtherapies,2024,24(1):284.
[7]WANGR,QUZ,LVY,etal.ImportantrolesofPI3K/AKTsignalingpathwayandrelevantinhibitorsinprostatecancerprogression[J].Cancermedicine,2024,13(21):e70354.
[8]TORTORELLAE,GIANTULLIS,SCIARRAA,etal.ARandPI3K/AKTinprostatecancer:ataleoftwointerconnectedpathways[J].InternationalJournalofMolecularScienc
es,2023,24(3):2046.
[9]PANDZICD,SUPICG,MISICD,etal.TheimpactofgeneticvariationsinretinoidXreceptoralphaontheriskandprognosisofHPV ‐negativeoralcarcinoma[J].EuropeanJournalofOralSc
iences,2025,133(3):e70015.
[10]CAOY,YIY,HANC,etal.NF-κBsignalingpathwayintumormicroenvironment[J].Frontiersinimmunology,2024,15:1476030.