槲皮素通过靶向结合ALDOA抑制肺癌细胞增长并促进凋亡  

Quercetin inhibits the growth of lung cancer cells and promotes cell apoptosis through targeted binding to aldolase A

作　　者：李丽芳 徐伟 吴树才[1] 刘欣燕[1] Li Lifang;Xu Wei;Wu Shucai;Liu Xinyan(Department of Oncology,Hebei Chest Hospital;Department of Oncology,Cangzhou People's Hospital)

机构地区：[1]河北省胸科医院肿瘤科,石家庄050041 [2]沧州市人民医院肿瘤科,沧州061000

出　　处：《重庆医科大学学报》2024年第12期1588-1593,共6页Journal of Chongqing Medical University

摘　　要：目的:观察槲皮素对人非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞A549生长抑制和凋亡的影响,筛选并验证槲皮素治疗肺癌相关靶蛋白,探讨槲皮素抗肿瘤的潜在机制。方法:使用浓度梯度槲皮素处理A549细胞,通过CCK8实验检测槲皮素对NSCLC细胞A549的增殖抑制作用,Annexin V/PI荧光染色法检测槲皮素对A549细胞凋亡的影响,Huprot^(TM)人全蛋白芯片筛选槲皮素潜在靶蛋白,ELISA实验验证槲皮素靶蛋白的相互作用,差示扫描荧光法(differential scanning fluorimetry,DSF)检测槲皮素对靶蛋白结构稳定性的影响。结果:A549细胞增殖抑制率呈槲皮素剂量依赖性,并且槲皮素处理后细胞凋亡率显著升高。通过人全蛋白芯片杂交获得279个槲皮素特异性结合蛋白,进一步使用DisGeNET数据库筛选出肺癌相关靶蛋白果糖二磷酸醛缩酶A(aldolase A,ALDOA)。ELISA实验和DSF检测结果表明槲皮素与ALDOA有特异性结合,并且这种结合会使ALDOA蛋白溶解温度(melting temperature,Tm)明显增大。结论:槲皮素通过抑制非小细胞癌细胞A549增殖、促进细胞凋亡,起到抗肺癌作用。其机制可能是槲皮素结合靶蛋白ALDOA并影响其蛋白结构,进而调控细胞糖代谢、激活凋亡相关通路。Objective:To investigate the effect of quercetin on the growth and apoptosis of non-small cell lung cancer(NSCLC)A549 cells,as well as the target proteins of quercetin associated with lung cancer and the potential mechanism of quercetin against lung cancer.Methods:NSCLC A549 cells were cultured and treated with gradient concentrations of quercetin.CCK8 assay was used to observe the inhibitory effects of quercetin on the proliferation of A549 cells;Annexin V/PI double staining was used to evaluate the effect of quercetin on the apoptosis of A549 cells;Huprot^(TM) Human Proteome Microarray was used to obtain the potential target proteins of quercetin;ELISA was used to validate the interaction between quercetin and target proteins;differential scanning fluorimetry(DSF)was used to observe the effect of quercetin on the structural stability of target proteins.Results:Quercetin significantly inhibited the proliferation of A549 cells in a dose-dependent manner,and there was a significant increase in the apoptosis rate of A549 cells treated with quercetin.A total of 279 specific binding proteins were obtained for quercetin by Huprot^(TM) Human Proteome Microarray,and aldolase A(ALDOA)was identified as the target protein associated with lung cancer based on DisGeNET database.ELISA and DSF assays confirmed the specific binding between quercetin and ALDOA,and such binding led to a significant increase in the melting temperature of ALDOA.Conclusion:Quercetin exerts an anti-lung cancer effect by inhibiting the proliferation of NSCLC cells and promoting cell apoptosis,possibly by binding to the target protein ALDOA and altering its structure,thereby regulating glucose metabolism and activating apoptosis-related pathways in cells.

关 键 词：槲皮素 肺癌 凋亡 果糖二磷酸醛缩酶A 

分 类 号：R932[医药卫生—生药学]