山柰酚调控PI3K/AKT信号通路对人肝癌HepG2细胞增殖、侵袭及迁移的抑制作用  

The inhibitory effects of kaempferol on the proliferation,invasion,and migration of human hepatocellular carcinoma HepG2 cells by modulating the PI3K/AKT signaling pathway

作　　者：刘鑫 刘波 孔令玉 LIU Xin;LIU Bo;KONG Lingyu(College of Public Health,Hebei University,Baoding,Hebei 071000,China;Hebei Mental Health Center,Hebei Sixth People's Hospital,Baoding,Hebei 071000,China;Center for Integrated Chinese and Western Medicine,North China University of Science and Technology Affiliated Hospital,Tangshan,Hebei 063000,China)

机构地区：[1]河北大学公共卫生学院,河北保定071000 [2]河北省第六人民医院(河北省精神卫生中心),河北保定071000 [3]华北理工大学附属医院中西医结合诊疗中心,河北唐山063000

出　　处：《安徽医药》2025年第5期903-908,共6页Anhui Medical and Pharmaceutical Journal

基　　金：河北省自然科学基金中医药联合基金(H2023209036);天津市卫生健康委中医中西医结合项目(2021130);河北省卫生健康委医学科研课题(20220696)。

摘　　要：目的探讨山柰酚对人肝癌细胞HepG2细胞的生长、迁移和侵袭的影响及其对磷酸肌醇3激酶(PI3K)、蛋白激酶B(AKT)、基质金属蛋白酶9(MMP-9)蛋白表达的调节的作用机制。方法2023年8―10月,利用生物信息学方法筛选肝癌基因与山柰酚药物靶点,筛选出山柰酚作用于肝癌的靶点。采用分子对接模拟山柰酚作用于肝癌靶点的分子过程;通过CCK-8法检测山柰酚对HepG2细胞存活率的影响;采用Transwell法检测HepG2细胞的侵袭和迁移能力;蛋白质印迹法检测信号通路相关蛋白PI3K、P-AKT、MMP-9表达水平的变化。结果山柰酚显著降低HepG2细胞的存活率(P<0.001),与对照组相比,不同浓度山柰酚组HepG2细胞存活率降低[(81.38±2.56)%、(78.22±4.69)%、(72.92±4.53)%、(66.45±1.44)%、(65.41±1.42)%、(62.83±2.79)%比(100.00±0.00)%];山柰酚能够明显抑制肝癌HepG2细胞的侵袭以及迁移能力(P<0.05),与对照组相比,侵袭数减少[(283.00±9.54)个、(232.00±26.46)个、(172.67±13.01)个比(652.00±85.85)个],迁移数减少[(512.00±28.58)个、(239.67±14.74)个、(102.00±29.00)个比(880.67±150.35)个];蛋白质印迹法结果表明经山柰酚能够下调PI3K、P-AKT、MMP-9蛋白表达水平(P<0.05)。结论山柰酚能够明显抑制HepG2细胞的增殖、侵袭和迁移,降低PI3K、P-AKT、MMP-9表达水平,其机制可能与山柰酚调控PI3K/AKT信号通路表达有关,为山柰酚治疗肝癌提供了一定的理论依据。Objective To investigate the effects of kaempferol on the growth,mobility,and infiltration of HepG2 human hepatocellular carcinoma cells,and its role in regulating the expression of PI3K,P-AKT,and MMP-9 proteins.Methods This study was conducted from August to October 2023,techniques in bioinformatics were employed to examine liver cancer genes,identify kaempferol's drug targets,and assess its impact on liver cancer.The molecular docking technique mimicked kaempferol's effect on liver cancer sites;Kaempferol's impact on HepG2 cell survival was measured using the CCK-8 assay;its invasive and migratory capabilities were identified through the Transwell assay;Variations in the levels of proteins associated with signaling pathways,which included PI3K,P-AKT,and MMP-9,were measured by Western blotting analysis.Results Kaempferol significantly reduced the survival rate of HepG2 cells(P<0.001),and compared with the control group,the survival rate of HepG2 cells was reduced in the different concentrations of kaempferol groups[(81.38±2.56)%,(78.22±4.69)%,(72.92±4.53)%,(66.45±1.44)%,(65.41±1.42)%,(62.83±2.79)%vs.(100.00±0.00)%];and kaempferol was able to significantly inhibit the invasion as well as the migration ability of hepatocellular carcinoma HepG2 cells(P<0.05),and the number of invasions was reduced compared with the control group(283.00±9.54,232.00±26.46,172.67±13.01 vs.652.00±85.85),and the number of migration was reduced 512.00±28.58,239.67±14.74,102.00±29.00 vs.880.67±150.35;the results of Western blotting showed that kaempferol was able to down-regulate the protein expression levels of PI3K,P-AKT,and MMP-9(P<0.05).Conclusions Kaempferol inhibits the growth,penetration,and movement of HepG2 cells,decreases the levels of PI3K,P-AKT,and MMP-9.This reduction might be linked to kaempferol's influence on the PI3K/AKT signaling pathway's expression,offering a theoretical foundation for treating hepatocellular carcinoma.

关 键 词：HEPG2细胞 山柰酚 肝癌 生长 机制研究 侵袭 迁移 

分 类 号：R285[医药卫生—中药学]