洋甘菊总黄酮抗宫颈鳞癌作用及机制研究  

Effect of Matricaria chamomilia total flavonoids against squamous cell carcinoma of the cervix and the underlying mechanism

作　　者：兰卫[1] LAN Wei(College of Traditional Chinese Medicine,Xinjiang Medical University,Xinjiang Urumqi 830017,China)

机构地区：[1]新疆医科大学中医学院,新疆乌鲁木齐830017

出　　处：《中国医院药学杂志》2025年第7期746-754,共9页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学地区基金项目(编号:81960771)。

摘　　要：目的:探讨洋甘菊总黄酮(Matricaria chamomilia total flavonoids,MCTF)防治宫颈鳞癌(squamous cell carcinoma,SCC)的可能作用机制。方法:以人宫颈癌SiHa细胞为模型,分为对照组、顺铂组(15μg·mL^(-1))、MCTF(25、50、100μg·mL^(-1))给药组,观察给药前后细胞形态变化;运用PI单染法及AnnexinV-FITC/PI双标记法研究MCTF对SiHa细胞周期和凋亡的影响;采用划痕实验,观察MCTF给药后细胞迁移的变化;结合酶联免疫吸附法测定细胞中肿瘤坏死因子(TNF-α)表达量;依据实时荧光定量PCR法检测CDK1、TYMS及TOP2A mRNA表达;同时蛋白免疫印迹实验检测细胞CDK1、TYMS、TOP2A、PI3K、Akt、p-PI3K、p-Akt、MDM2、p53、p21及MMP2/9、Bax、Bcl-2蛋白表达水平。结果:体外细胞实验表明,MCTF各给药组可以不同程度地抑制SiHa细胞增殖,促进细胞凋亡,使SiHa细胞阻滞在G0/G1期,抑制细胞迁移,降低SiHa细胞TNF-α因子水平(P<0.01);MCTF各给药组可通过下调SiHa细胞中CDK1、TYMS、TOP2A的mRNA表达量(P<0.01),下调MMP-2、MMP-9、MDM2、CDK1、TYMS、TOP2A、Bcl-2以及p-PI3K/PI3K、p-Akt/Akt的蛋白表达水平(P<0.01),上调Bax、p53、p21的蛋白表达水平(P<0.01),从而调控PI3K-Akt-p53通路及细胞凋亡途径促进SiHa的凋亡和抑制增殖。结论:MCTF可能通过调控PI3K-Akt-p53通路及其介导的细胞凋亡途径促进SiHa细胞凋亡和抑制增殖,进而发挥防治SCC的作用,为临床应用提供基础。OBJECTIVE To explore the potential effects of Matricaria chamomilia total flavonoids(MCTF)against squamous cell carcinoma(SCC)of the cervix.METHODS Human cervical cancer cell line SiHa was used in the in vitro experiments.SiHa cells were induced with blank control,15μg·mL^(-1)cisplatin,and 15μg·mL^(-1)cisplatin+25,50 and 100μg·mL^(-1)MCTF.The morphological changes of cells before and after administration were observed.The effects of MCTF on SiHa cell cycle and apoptosis were studied by PI single staining and AnnexinV-FITC/PI double labeling,respectively.Scratch test was used to observe the changes in cell migration after MCTF administration.The expression of tumor necrosis factor alpha(TNF-α)was detected by enzyme-linked immunosorbent assay.The mRNA levels of cyclin-dependent kinases 1(CDK1),thymidylate synthetase(TYMS)and topoisomeraseⅡalpha(TOP2A)were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Protein levels of CDK1,TYMS,TOP2A,phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),p-PI3K,p-Akt,murine double minute 2(MDM2),p53,p21,matrix metalloproteinase-2/9(MMP2/9),and Bcl-2-associated X(Bax)/B-cell lymphoma 2(Bcl-2)were detected by Western blot.RESULTS In vitro cell experiments showed that MCTF at either concentration significantly inhibited cell proliferation and migration,induced cell apoptosis,arrested cell cycle progression in the G0/G1 phase,and reduced the secretion of TNF-αto varying degrees(P<0.01).MCTF induction significantly downregulated mRNA levels of CDK1,TYMS and TOP2A,and protein levels of MMP-2,MMP-9,MDM2,CDK1,TYMS,TOP2A,Bcl-2,p-PI3K/PI3K,and p-Akt/Akt,upregulated protein levels of Bax,p53 and p21 in cisplatin-induced SiHa cells(all P<0.01).Overall,MCTF promoted the apoptosis and inhibited the progression of SiHa cells by the PI3K-Aktp53 signaling pathway.CONCLUSION MCTF promotes the apoptosis and inhibits the progression of SiHa cells by the PI3KAkt-p53 signaling pathway,thus preventing and treating SCC of the cervix.Our findings provide re

关 键 词：洋甘菊总黄酮 宫颈鳞癌 抗癌作用 PI3K-Akt-p53通路 

分 类 号：R282[医药卫生—中药学] R932[医药卫生—中医学]