黄芩素联合5-FU调控ROS/MAPK信号通路对H446肺癌细胞生物学行为的作用研究  

Effect of baicalein combined with 5-FU on proliferation,apoptosis and migration of H446 cells by regulating ROS/MAPK signaling pathway

作　　者：郑涵予[1] 李艳丽[1] 杨菊菊 崔伟建[1] Zheng Hanyu;Li Yanli;Yang Juju;Cui Weijian(Department of Respiratory Intervention,the First People’s Hospital of Shangqiu,Shangqiu 476000,China)

机构地区：[1]商丘市第一人民医院呼吸介入科,商丘476000

出　　处：《中华内分泌外科杂志》2022年第2期231-236,共6页Chinese Journal of Endocrine Surgery

基　　金：2018年度河南省医学科技攻关计划(2018020953)。

摘　　要：目的探索黄芩素(baicalein,BAI)联合5-FU对小细胞肺癌H466细胞增殖、凋亡及迁移的影响,并进一步探索其增敏机制。方法体外培养H466肺癌细胞,并分成对照组、BAI组、5-FU组和联合处理组;利用CCK-8实验检测各组细胞存活率;利用流式细胞术检测细胞凋亡情况和ROS水平变化情况;利用Western blot实验检测MAPK通路蛋白表达量变化情况。结果CCK-8结果中,4组细胞处理24 h后存活率依次为114.3%±2.8%,79.8%±3.4%,57.6%±1.8%,40.3%±2.7%,与其他3组相比,联合处理组对H446细胞的增殖抑制效果更强,差异有统计学意义(P<0.001);联合处理组凋亡的H446细胞比例为49.2%±3.8%,与5-FU单独处理组33.9%±4.3%相比,差异有统计学意义(P<0.001);联合处理组对H446细胞迁移的抑制率高于5-FU单独处理组,差异有统计学意义(P<0.001);黄芩素和5-FU联合处理能上调H446细胞中的ROS水平,进而调节MAPK信号通路。结论黄芩素与5-FU联合使用能通过上调肺癌H446细胞中的ROS水平,激活JNK及p38信号通路,抑制ERK信号通路,进一步增强5-FU对H446细胞的增殖抑制、诱导凋亡及抑制迁移作用,为黄芩素在小细胞肺癌中的应用提供了一定的实验依据。Objective To investigate the effects of baicalein combined with 5-FU on the proliferation,apoptosis and migration of small cell lung cancer H466 cells,and further to explore its sensitization mechanism.Methods H466 cells were cultured in vitro and divided into blank control group,baicalein single treatment group,5-FU single treatment group and combined treatment group.CCK-8 experiment was used to detect cell survival rate in each group;Flow cytometry was used to detect cell apoptosis and changes in ROS levels;Western blot was used to detect changes in the protein expression of the MAPK pathway.Results CCK-8 results showed that the survival rates of the four groups of cells after 24 h treatment were 114.3%±2.8%,79.8%±3.4%,57.6%±1.8%,and 40.3%±2.7%.Compared with the other three groups,the combined treatment group had stronger inhibitory effect on the proliferation of H446 cells,and the difference was statistically significant(P<0.001).The proportion of apoptotic H446 cells in the combined treatment group was 49.2%±3.8%,which was significantly different from 33.9%±4.3%in the 5-FU single treatment group,and the difference was statistically significant(P<0.001).The inhibition rate of H446 cell migration in the combined treatment group was higher than that in the 5-FU single treatment group,and the difference was statistically significant(P<0.001).Combined treatment of baicalein and 5-FU can up-regulate ROS levels in H446 cells,thereby regulating the MAPK signaling pathway.Conclusion The combined use of baicalein and 5-FU can increase the level of ROS in lung cancer H446 cells,activate the JNK and p38 signaling pathways,inhibit the ERK signaling pathway,and enhance 5-FU's proliferation inhibition,apoptosis induction and migration inhibition effects on H446 cells,which provides a certain experimental basis for the application of baicalein in small cell lung cancer.

关 键 词：黄芩素 小细胞肺癌H446细胞 5-氟尿嘧啶 活性氧 MAPK信号通路 

分 类 号：R73[医药卫生—肿瘤]