芒柄花黄素对非小细胞肺癌A549荷瘤裸鼠肿瘤组织细胞凋亡的影响及其机制  

Effect of formononetin on apoptosis of tumor cells in non-small cell lung cancer A549 nude mice and its mechanism

作　　者：张丽君 欧逢莲 张焱 黄国玉 肖纪余 刘青阳 许光亚 ZHANG Lijun;OU Fenglian;ZHANG Yan;HUANG Guoyu;XIAO Jiyu;LIU Qingyang;XU Guangya(College of Pharmacy,Dali University,Yunnan Dali 671003,China;School of Basic Medicine,Chengdu University,Sichuan Chengdu 610083,China)

机构地区：[1]大理大学药学院,云南大理671003 [2]成都大学基础医学院,四川成都610083

出　　处：《中药与临床》2025年第1期23-28,共6页Pharmacy and Clinics of Chinese Materia Medica

摘　　要：目的:研究芒柄花黄素对人非小细胞肺癌A549所致荷瘤裸鼠肿瘤组织细胞凋亡及相关Bax、Bcl-2、Caspase-3蛋白表达的影响。方法:将采用皮下接种A549细胞建立的A549荷瘤小鼠随机分为模型组、阳性对照组(环磷酰胺20 mg·kg^(-1))及芒柄花黄素高、中、低剂量组(80、40、20 mg·kg^(-1)),每天灌胃给药,持续3周。测定各组裸鼠肿瘤组织大小并计算其体积,Tunel荧光染色和流式细胞术分析肿瘤组织细胞凋亡情况,RT-qPCR和Western blot检测凋亡相关因子Bax、Bcl-2、Caspase-3蛋白及mRNA表达水平。结果:与模型组比较,各浓度芒柄花黄素呈剂量依赖性降低裸鼠肿瘤体积(P<0.05);促进了肿瘤组织细胞的凋亡(P<0.05)。芒柄花黄素高剂量组(80 mg·kg^(-1))显著增加组织中Bax、Caspase-3蛋白及mRNA表达,降低Bcl-2蛋白及mRNA表达(P<0.05)。结论:芒柄花黄素能显著抑制A549荷瘤裸鼠肿瘤组织的生长,其作用机制与降低抗凋亡蛋白Bcl-2的表达、促进促凋亡蛋白Bax和Caspase-3的表达有关。Objective:To investigate the effect of formononetin on cell apoptosis and expressions of Bax,Bcl-2 and Caspase-3 in tumor tissues of nude mice induced by human non-small cell lung cancer A549.Methods:A549 tumor-bearing mice established by subcutaneous inoculation of A549 cells were randomly divided into model group,positive control group(cyclophosphamide,25 mg·kg^(-1)),and formononetin high,medium and low dose groups(80 mg·kg^(-1),40 mg·kg^(-1),20 mg·kg^(-1)).The mice were administrated by gavage every day for 3 weeks.The tumor tissue size was measured and its volume was calculated.Tunel staining was used to observe the apoptosis of tumor tissue.Flow cytometry was used to analyze the apoptosis rate of tumor tissue related cells,and RT-qPCR and Western blot were used to detect the protein and mRNA expression levels of apoptosis-related factors Bax,Bcl-2 and Caspase-3.Results:Compared with the model group,the tumor volume of nude mice was decreased in a dose-dependent manner by each concentration of formononetin(P<0.05).Formononetin promoted the apoptosis of tumor cells(P<0.05).The expressions of Bax and Caspase-3 protein and mRNA were significantly increased in high-dose group(80 mg·kg^(-1)),whereas the expressions of Bcl-2 protein and mRNA were decreased(P<0.05).Conclusion:Formononetin can significantly inhibit the growth of tumor tissue in A549 tumor-bearing nude mice.The mechanism of action is related to reducing the expression of anti-apoptotic protein Bcl-2 and promoting the expression of pro-apoptotic proteins Bax and Caspase-3.

关 键 词：芒柄花黄素 人非小细胞肺癌 BAX蛋白 BCL-2蛋白 CASPASE-3蛋白 

分 类 号：R285.5[医药卫生—中药学]