Lupalbigenin通过EGFR信号通路抑制非小细胞肺癌NCI-H1975细胞增殖  

Lupalbigenin inhibits proliferation of NCI-H1975 cell in non-small cell lung cancer through the EGFR signaling pathway

作　　者：李思雨 黄艳苹[1] 朱威巍 杨星莹 盛军[1] 王宣军[1] LI Siyu;HUANG Yanping;ZHU Weiwei;YANG Xingying;SHENG Jun;WANG Xuanjun(Key Laboratory of Pu-er Tea Science and Technology,Yunnan Agricultural University,Yunnan Kunming 650201,China;College of Food Science and Techonology,Yunnan Agricultural University,Yunnan Kunming 650201,China)

机构地区：[1]云南农业大学普洱茶学教育部重点实验室,云南昆明650201 [2]云南农业大学食品科学技术学院,云南昆明650201

出　　处：《现代肿瘤医学》2024年第9期1621-1626,共6页Journal of Modern Oncology

基　　金：云南省基础研究专项青年项目(编号:202001AU070125);云南省农业联合专项面上项目(编号:202301BD070001-098)。

摘　　要：目的:探究Lupalbigenin是否通过表皮生长因子受体(epidermal growth factor receptor,EGFR)信号通路诱导非小细胞肺癌(non-small cell lung cancer,NSCLC)系中NCI-H1975细胞增殖。方法:主要采用了MTT法检测细胞毒性;用细胞形态学观察、细胞迁移实验、细胞克隆形成实验观察及检测细胞增殖能力;通过蛋白质免疫印迹法(Western Blot)检测Lupalbigenin对EGFR和其下游MAPK信号通路蛋白ERK及其磷酸化水平及其凋亡相关Cleaved PARP、P21、CDK4、CDK6、CyclinD1和CyclinA2以及抗凋亡蛋Bcl-2的影响。结果:结果显示Lupalbigenin在NCI-H1975细胞系上IC_(50)值为3.246μmol/L,并且呈浓度依赖性抑制细胞增殖;细胞形态学观察结果显示与空白组比较,10μmol/L Lupalbigenin实验组处理细胞24 h导致细胞核固缩、细胞质凝聚及细胞凋亡显著增加;迁移实验和集落形成实验结果显示,5μmol/L LG能够显著抑制细胞迁移和菌落形成能力;Western Blot检测结果表明,Lupalbigenin在较短时间内对EGFR/ERK蛋白磷酸化表达有显著的抑制作用。同时,Lupalbigenin处理后,Cleaved PARP和P21蛋白的表达水平显著上调,CDK4、CDK6、CyclinD1和CyclinA2以及Bcl-2蛋白的表达水平显著下降。结论:综上,Lupalbigenin可以调控EGFR及其下游相关蛋白的表达,从而抑制NCI-H1975细胞的增殖。Objective:To investigate whether Lupalbigenin induces the proliferation of NCI-H1975 cells in non-small cell lung cancer(NSCLC)through epidermal growth factor receptor(EGFR)signaling pathway.Methods:MTT assay was used to detect cytotoxicity.Cell proliferation ability was observed and measured by cell morphology,cell migration and cell clonal formation.Western Blot was detected the effects Lupalbigenin of on EGFR and its downstream MAPK signaling pathway protein ERK and its phosphorylation levels,and the levels of apoptosis related proteins cleaved PARP,P21,CDK4,CDK6,CyclinD1,CyclinA2 and the levals of anti-apoptotic protein Bcl-2.Results:The IC_(50)value of Lupalbigenin in NCI-H1975 cell line was 3.246μmol/L,and Lupalbigenin inhibited cell proliferation in a concentration-dependent way.The results of cell morphology showed that compared with the blank group,24 h treatment of 5μmol/L Lupalbigenin experimental group resulted in a significant increase in nuclear shrinkage,cytoplasmic aggregationand cell apoptosis.Migration and colony formation experiments showed that 5μmol/L LG could significantly inhibit cell migration and colony formation.Western Blot analysis showed that Lupalbigenin significantly inhibited the phosphorylation of EGFR/ERK protein in a short period of time.Meanwhile,after Lupalbigenin treatment,Cleaved PARP and P21 protein expression levels were significantly up-regulated,and CDK4,CDK6,CyclinD1,CyclinA2,and Bcl-2 protein expression levels were significantly decreased.Conclusion:In conclusion,Lupalbigenin can regulate the expression of EGFR and its downstream related proteins,thereby inhibiting the proliferation of NCI-H1975 cells.

关 键 词：Lupalbigenin EGFR NCI-H1975细胞 增殖抑制 

分 类 号：R734.2[医药卫生—肿瘤]