双术汤通过P53/SLC7A11/GPX4通路诱导胃癌细胞铁死亡

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Shuangshu Decoction inhibits growth of gastric cancer cell xenografts by promoting cell ferroptosis via the P53/SLC7A11/GPX4 axis

CHENXinyuan，Whengting，uidi²，NXueqin，ZHANGodan³，AOJunyu，I2 Guangxisityeicii;ttedsteot AfiliatedHsialgiieulyei UniersityofnseedicinengO9na;GangiKeyLboatoryofasatioaledicineforeatinggdence Infectiousiseaseswithntegratiueedicine，anning99，in

Abstract：ObjectiveToexplorethemechanismofShuangshuDecoction（SSD）forinhibitinggrowthofgastriccancerxenografts innudemice.Methods Networkpharmacologyanalysis wasconducted toidentifythecommon targetsofSSDandgastric cancercellferroptosis，andbioinformaticsanalysisandmoleculardockingwereusedtovalidatethecoretargets.Inecell experimentGeleatditiaed，-（oisit）dgel viability， ferroptosis markers （ROs， Fe2+ and GSH）， expressions of P53， SLC7A11 and GPX4，and mitochondrial morphology wereexamined.Inanudemouse model bearinggastriccancer xenografts，theeffectsof gavage with SSD，intraperitoneal injectionofFe-oiroareeightsolodpiosofdG4 levelswereevaluated.ResultsTheactivecomponentsinSSD（quercetinandwogonin）showedstrongbindingaffinitiesto P53.InAGScels，SSD treatment dose-dependentlyinhibitedcellproliferation，increasedOSand Fe2+ levels， upregulated P53 expression，andoweglatedteexpresiosofandGX4utteeectsreeectivelyadFe1 treatment.SSDalsoinduced mitochondrialshrinkageandincreasedthemembranedensitywhichwerealleviatedbyer-1.In the tumor-bearing mouse models，gavage withSSDsignificantlyreducedtumor sizeand weight，causedtumorcellnecrosis， upregulated P53 and downregulated SLC7A1 and GPX4 expression inthe tumor tissue，and these effcts wereobviously mitigatedbyFer-1treatment.ConclusionSSDinhibits gastriccancer growth innudemicebyinducing cellferroptosis viathe P53/SLC7A11/GPX4 axis.

Keywords：gastricancer;tworkaacologyiioratics;oleculardocing;uangshuDecoction;erroosis;5 SLC7A11/GPX4 pathway

胃癌是全球高发的消化道恶性肿瘤1，在中国尤为高发2]。（剩余16455字）