首页|期刊导航|湖北医药学院学报|木犀草素调控Notch信号通路抑制非小细胞肺癌细胞恶性进展

木犀草素调控Notch信号通路抑制非小细胞肺癌细胞恶性进展OA

Luteolin Inhibits Malignant Progression of Non-small Cell Lung Cancer Cells by Regulating Notch Signaling Path-way

中文摘要英文摘要

目的:探究木犀草素在抑制非小细胞肺癌(NSCLC)细胞恶性增殖方面的作用,同时验证该抑制作用是否经由调控Notch信号传导途径来实现.方法:本实验采用木犀草素处理人NSCLC细胞.细胞增殖活力利用CCK-8 试剂盒进行量化评估,细胞凋亡状态通过Hoechst 33258 染色/流式细胞技术监测.采用Western blot方法检测凋亡相关蛋白以及 Notch 信号传导通路中蛋白的表达水平.在木犀草素处理基础上给予 Notch 通路激活剂(Jagged1)处理来验证木犀草素调控Notch信号通路对细胞生物学行为的影响.结果:⑴木犀草素干预A549、NCI-H292、NCI-H596、SK-MES-1 和NCI-H460 五种NSCLC细胞24、48 h后,细胞活力均降低,且木犀草素浓度越高,干预时间越长,作用效果越明显.其中,A549 细胞最为敏感,因此选择其作为后续研究的实验对象;⑵20、40、80 μmol/L木犀草素处理A549 细胞 24 h.Hoechst 33258 染色和蛋白表达分析显示,木犀草素可促进A549 细胞凋亡,上调caspase-3、caspase-9 及Bax蛋白表达,下调Bcl-2 蛋白表达.同时,木犀草素还能抑制Notch通路蛋白Notch1和HES1 的表达,且高剂量的木犀草素抑制作用更为显著.加入Notch激活剂Jagged1 后,木犀草素对Notch信号通路的抑制作用被解除,A549 细胞存活率上升,凋亡率降低,caspase-3、caspase-9 及Bax蛋白表达下调,Bcl-2 蛋白表达增加.结论:木犀草素能够通过调控Notch信号通路,阻碍细胞增殖及促进细胞凋亡的发生来抑制NSCLC细胞的恶性发展.

Objective To investigate the role of luteolin in inhibiting malignant proliferation of non-small cell lung cancer(NSCLC)cells and to verify whether this inhibitory effect is mediated by regulating the Notch signaling pathway.Methods In this experiment,human NSCLC cells were treated with luteolin.Cell proliferation activity was quantitatively evaluated u-sing the CCK-8 assay kit,while cell apoptosis was monitored using Hoechst 33258 staining and flow cytometry.Western blot was performed to detect the expressions of apoptosis-related proteins and those in the Notch signaling pathway.Subse-quently,a Notch pathway activator(Jagged1)was administered alongside luteolin treatment to assess the impact of luteolin on cellular biological behavior via the Notch signaling pathway.Results After 24 and 48 h of treatment with luteolin,cell viability was reduced in A549,NCI-H292,NCI-H596,SK-MES-1,and NCI-H460 cells,with the effects becoming more pronounced as the concentration of luteolin increased and the intervention time extended.A549 cells were the most sensitive and were chosen for further study;they were treated with luteolin at three concentrations(20,40,80 μmol/L)for 24 h.Hoechst 33258 staining and protein expression analysis indicated that luteolin promoted the apoptosis in A549 cells by up-regulating caspase-3,caspase-9,and Bax while down-regulating Bcl-2.Additionally,luteolin inhibited the pro-teins in the Notch signaling pathway Notch1 and HES1,and the inhibition was more significant under higher concentration.Following the addition of Jagged1,the inhibitory effect of luteolin on the Notch signaling pathway was diminished,which led to an increase in A549 cell survival,a decrease in apoptosis,down-regulations of caspase-3,caspase-9,and Bax,and an increase in Bcl-2.Conclusion Luteolin can inhibit the malignant progression of NSCLC cells by regulating the Notch signaling pathway,which hinders cell proliferation and promotes apoptosis.

李嘉;杨莉莉;韩芳;李军

皖北卫生职业学院药学系皖北卫生职业学院临床医学系,安徽 宿州 234000皖北卫生职业学院药学系山东第一医科大学药学系,山东 济南 250200

木犀草素NSCLC增殖凋亡Notch信号通路

LuteolinNon-small cell lung cancer(NSCLC)ProliferationApoptosisNotch signaling pathway

《湖北医药学院学报》 2025 (3)

265-271,7

安徽省高校自然科学基金重点项目(2023AH053128)

10.13819/j.issn.2096-708X.2025.03.003

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