桂枝茯苓丸活性成分常春藤皂苷元通过抑制JAK2/STAT3通路抑制宫颈癌细胞的生长

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Therapeutic mechanism of hederagenin， an active component in Guizhi Fuling Pellets， against cervical cancer in nude mice

ZHU Yinfu，LI Yirant，WANGYi’，HUANG Yinger²，GONG Kunxiang3，HAO Wenbo，UNLingling4 choolfbodoooolticali 3InstituteofReproductieHealthnderinatologyGuangzou WomenandCidren'sedicalCenterGuangoudicality Guangzhoi;eteteaedosldiileciethdica Guangzhou，ina

Abstract：ObjectiveToexplorethetherapeuticmechanismofGuizhiFuling（GZFL）Peletsagainstcervicalcancer.Methods Publiclyavailabledatabases wereusedtoidentifythe targetsof GZFLPeletsandcervicalcancertoconstructthe proteinprotein interaction （PPI）network，followedbyGObiological processandKEGG pathwayenrichmentanalysisof thehub genes.The "Traditional Chinese Medicine-ActiveIngredients-Targets-Pathways”networkforGZFLPeletsincervicalancer treatment was generatedusing Cytoscapev10.0.0，andmoleculardocking ofthedrugand potential targets wasperformed to predictthespecifictargetsofactivecomponentsinGuizhiFuling Pelets.Theinhibitory effectsofhederagenin，anactive ingredient in GZFLPelets，was tested incultured cervical cancercelsand innude mice bearing cervicalcancerxenografts. ResultsGZFLPeletscontain33activecomponents targeting247actionsites.Atotalof1017cervicalcancer-relatedtargets wereobtained，andamongthem195wereidentifiedaspotentialtherapeutictargetsofGZFLPeletsforcericalcancer treatment，includingthekeyargetsofGABRA1，K2，JAK2，H3A，GSRndIL-17.oleculardockingstudysowedlow bindingenergiesoftheactivecomponentssuchashederagenin，campesterol，andstigmasterolforprotein-molecule interaction. GOenrichmentanalysis suggestedthatGZFLPellets inhibitedcervicalcancer primarilybyregulating responses to steroidhormonesiativetre，andlipopolysacchides.AmongtheactiveomponentsofGZFLPelletsdeagewa foundtoinhibitcervicalcancecelsinitroandsignificantlyreducedSAT3phosphorylationlevelinthecancerces.Iude micebearingcervicalcancerxenografts，hederagenineffectivelyinhibitedtumorgrowthratewithoutcausingobviousadverse efects.ConclusionGZFLPelletsinhibitcervicalcancercellgrowththroughitsmultipleactivecomponentsthattargetdierent pathways. Among these components，hederagenininhibits tumor cellgrowth posibly bydirectly binding to JAK2proteinto inhibit STAT3 phosphorylation.

Keywords： network pharmacology; Guizhi Fuling Pellets; cervical cancer;HPV infection; hederagen

宫颈癌是全球女性常见的妇科恶性肿瘤，2020年全球新发病例约60万，死亡34万，位居女性癌症死亡率第4位1，其主要病理类型为宫颈鳞状细胞癌（占比85% ）和宫颈腺癌（占比 10%～12% [2]。（剩余18015字）