菊苣酸通过FOXO3-FOXM1信号轴抑制肺癌细胞增殖和化疗敏感性并促进凋亡  

Cichoric acid inhibits lung cancer cell proliferation and chemotherapy sensitivity and promotes apoptosis through the FOXO3-FOXM1 signal axis

作　　者：刘杰[1] 李新建[1] 江盼 焦宇知[1] LIU Jie;LI Xinjian;JIANG Pan;JIAO Yuzhi(School of Food,Jiangsu Food and Drug Vocational and Technical College,Jiangsu Huai'an 223001,China)

机构地区：[1]江苏食品药品职业技术学院食品学院,江苏淮安223001

出　　处：《现代肿瘤医学》2024年第2期248-254,共7页Journal of Modern Oncology

基　　金：江苏省高等学校自然科学研究重大项目(编号:21KJA350001)。

摘　　要：目的:研究菊苣酸调节叉头框蛋白O3(FOXO3)-叉头蛋白M1(FOXM1)信号轴对肺癌细胞增殖、凋亡和化疗敏感性的影响。方法:构建人肺癌细胞顺铂(DDP)耐药细胞A549/DDP,用不同浓度菊苣酸处理后通过MTT法测定细胞活力,以不显著降低细胞活力的最大浓度作为菊苣酸的最佳作用浓度。将A549细胞随机分为对照组、空载组、菊苣酸组、菊苣酸+FOXO3敲低组,分组处理后分别采用MTT法、集落生成实验及流式细胞实验测定各组A549细胞增殖及凋亡;采用免疫印迹法检测各组A549细胞FOXO3-FOXM1通路、增殖(PCNA)与凋亡(Bcl-2、Bax)相关蛋白表达。将A549/DDP细胞随机分为对照组、DDP组、DDP+空载组、DDP+菊苣酸组、DDP+菊苣酸+FOXO3敲低组,分组处理后分别采用MTT法、集落生成实验及流式细胞实验测定各组A549/DDP细胞增殖及凋亡;采用免疫印迹法检测各组A549/DDP细胞FOXO3-FOXM1通路、增殖、耐药[P-糖蛋白(P-gp)]与凋亡相关蛋白表达。结果:与对照组相比,空载组A549细胞各指标无明显变化(P>0.05);菊苣酸组A549细胞凋亡率、Bax与FOXO3蛋白表达升高(P<0.05),集落生成率、细胞活力、Bcl-2与PCNA、FOXM1蛋白表达降低(P<0.05);FOXO3敲低可减弱菊苣酸对A549细胞上述各指标的作用。与对照组、DDP组相比,DDP+空载组A549/DDP细胞各指标均无明显变化(P>0.05);DDP+菊苣酸组A549/DDP细胞凋亡率、Bax与FOXO3蛋白表达均升高(P<0.05),集落生成率、细胞活力、Bcl-2与PCNA、P-gp、FOXM1蛋白表达均降低(P<0.05);FOXO3敲低可减弱菊苣酸对DDP处理下A549/DDP细胞上述各指标的作用。结论:菊苣酸可通过激活FOXO3-FOXM1信号而抑制肺癌细胞增殖和化疗敏感性并促进其凋亡,进而增强化疗药物DDP对其DDP耐药细胞的杀伤作用。Objective:To investigate the impacts of cichoric acid on proliferation,apoptosis,and chemotherapy sensitivity of lung cancer cells by regulating the forkhead box O3(FOXO3)-forkhead protein M1(FOXM1)signal axis.Methods:Cisplatin(DDP)resistant human lung cancer cell line A549/DDP was constructed and treated with different concentrations of cichoric acid.Cell viability was determined by MTT assay.The maximum concentration that did not significantly reduce cell viability was used as the optimal concentration of cichoric acid.A549 cells were randomly separated into a control group,an empty group,a cichoric acid group,and a cichoric acid+FOXO3 knockdown group.After grouping,MTT assay,colony formation assay,and flow cytometry were applied to determine the proliferation and apoptosis of A549 cells in each group.Immunoblotting was applied to detect the expression of FOXO3-FOXM1 pathway,proliferation(PCNA),and apoptosis(Bcl-2,Bax)related proteins in A549 cells in each group.A549/DDP cells were randomly separated into control group,DDP group,DDP+empty group,DDP+cichoric acid group,and DDP+cichoric acid+FOXO3 knockdown group.After grouping,MTT assay,colony formation assay,and flow cytometry were applied to determine the proliferation and apoptosis of A549/DDP cells in each group.Immunoblotting was applied to detect the expression of FOXO3-FOXM1 pathway,proliferation,resistance[P-glycoprotein(P-gp)],and apoptosis related proteins in A549/DDP cells in each group.Results:Compared with the control group,there was no obvious change in all indicators of A549 cells in the empty group(P>0.05).The apoptosis rate of A549 cells and the expression of Bax and FOXO3 proteins in the cichoric acid group increased(P<0.05),the colony formation rate,cell viability,and the expression of Bcl-2,PCNA,FOXM1 proteins reduced(P<0.05).Knocking down FOXO3 can weaken the effect of cichoric acid on the above indicators in A549 cells.Compared with the control group and DDP group,there was no obvious change in various indicators of A549/DDP cells in the DD

关 键 词：菊苣酸 FOXO3-FOXM1 肺癌 增殖 凋亡 化疗敏感性 

分 类 号：R734.2[医药卫生—肿瘤]