首页|湖北枫杨总黄酮对非小细胞肺癌A549细胞迁移、侵袭和铁死亡的影响

湖北枫杨总黄酮对非小细胞肺癌A549细胞迁移、侵袭和铁死亡的影响

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目的:探究湖北枫杨总黄酮对非小细胞肺癌A549细胞迁移与侵袭及铁死亡的影响及机制.方法:将A549细胞分为:对照组,低、中、高剂量(100、150和200 μg/mL)枫杨总黄酮组,铁死亡抑制剂liproxstatin-1(Lip-1)组,Lip-1+高剂量枫杨总黄酮组.采用CCK-8法检测细胞活力;划痕实验和Transwell实验检测细胞迁移及侵袭能力;谷胱甘肽(GSH)试剂盒检测细胞脂质过氧化水平;RT-qPCR检测细胞溶质载体家族7成员11(SLC7A11)和谷胱甘肽过氧化物酶4(GPX4)的mRNA水平;Western blot检测SLC7A11、GPX4、Kelch样环氧氯丙烷相关蛋白1(Keap1)、核因子E2相关因子2(Nrf2)和血红素加氧酶1(HO-1)的蛋白表达水平.结果:与对照组相比,各剂量枫杨总黄酮组A549细胞活力降低(P<0.01),迁移及侵袭能力降低(P<0.01),GSH含量显著降低(P<0.01),SLC7A11和GPX4 mRNA及蛋白表达水平显著降低(P<0.01),Nrf2和HO-1蛋白表达水平显著降低(P<0.01),Keap-1蛋白表达水平升高(P<0.01);加入铁死亡抑制剂后,与高剂量枫杨总黄酮组相比,A549细胞活力显著升高(P<0.01),SLC7A11、GPX4、Nrf2、HO-1蛋白表达水平升高,Keap-1蛋白表达水平下降(P<0.01).结论:湖北枫杨总黄酮能抑制A549细胞迁移与侵袭并且通过调控Keap-1/Nrf2/HO-1通路诱导肺癌A549细胞铁死亡.
Effects of total flavonoids of Pterocarya hupehensis Skan on migration,invasion and ferroptosis of non-small-cell lung cancer A549 cells
AIM:To investigate the impact of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on the migration,invasion,and ferroptosis of non-small-cell lung cancer A549 cells.METHODS:The A549 cells were divided into control group,low-,medium-and high-dose(100,150 and 200 μg/mL)PHSTF groups,ferroptosis inhibitor liprox-statin-1(Lip-1)group,and high-dose PHSTF combined with Lip-1 group,each cultured in corresponding media.Cell via-bility was assessed using the CCK-8 assay,while cell migration and invasion abilities were determined through scratch and Transwell assays.Cell lipid peroxidation levels were measured using the glutathione(GSH)assay kit.RT-qPCR was em-ployed to assess the mRNA expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while Western blot was utilized to examine the protein expression of SLC7A11,GPX4,Kelch-like epichlorohy-drin-associated protein-1(Keap-1),nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1).RE-SULTS:Compared with control group,PHSTF significantly diminished the viability of A549 cells in a time-and dose-de-pendent manner(P<0.01),and the cell migration and invasion were also reduced(P<0.01),along with a significant de-crease in GSH level(P<0.01).Treatment with PHSTF inhibited the mRNA and protein expression levels of ferroptosis-re-lated proteins,including SLC7A11 and GPX4(P<0.01),suppressed the protein expression of Nrf2 and HO-1(P<0.01),and enhanced the expression of Keap-1(P<0.01).The Lip-1 partially restored the decrease in cell viability in-duced by PHSTF(P<0.01),significantly up-regulated the protein expression levels of SLC7A11,GPX4,Nrf2 and HO-1,and suppressed the protein expression of Keap-1(P<0.01).CONCLUSION:Total flavonoids of Pterocarya hupehen-sis Skan can inhibit the migration and invasion of non-small-cell lung cancer A549 cells,and induce the cell ferroptosis by regulating the Keap-1/Nrf2/HO-1 pathway.

Total flavonoids of Pterocarya hupehensis Skannon-small-cell lung cancerferroptosisKeap-1/Nrf2/HO-1 pathway

陈国庆、董倩男、杨锐、高瑛、刘人嘉、袁林、向阳、吴昊

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湖北恩施学院医学部,湖北 恩施 445000

湖北民族大学风湿性疾病发生与干预湖北省重点实验室,湖北 恩施 445000

湖北恩施学院附属恩施慧宜中西医结合风湿医院,湖北 恩施 445000

湖北枫杨总黄酮 非小细胞肺癌 铁死亡 Keap-1/Nrf2/HO-1通路

国家自然科学基金资助项目湖北省自然科学基金一般面上项目湖北省教育厅科学研究指导性项目恩施州土家族苗族自治州科技局资助项目

819607762022CFB515B2022495JCY20211000040

2024

中国病理生理杂志
中国病理生理学会

中国病理生理杂志

CSTPCD北大核心
影响因子:1.065
ISSN:1000-4718
年,卷(期):2024.40(2)
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