恩沃利单抗通过下调SLC1A3/ERK/MAPK信号通路抑制AGS胃癌细胞生长  

Envafolimab inhibits the growth of AGS gastric cancer cells by down-regulating SLC1A3/ERK/MAPK signaling pathway

作　　者：董转霞 李峰[2] 王育生 DONG Zhuan-xia;LI Feng;WANG Yu-sheng(The First Affiliated Hospital of Shanxi Medical University,Taiyuan 030001,China;Central laboratory,Shanxi Cancer Hospital,Taiyuan 030013,China;Department of Oncology and Gastroenterology,the First Affiliated Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学附属第一医院,030001 [2]山西省肿瘤医院中心实验室,030013 [3]山西医科大学第一医院肿瘤消化科,030001

出　　处：《现代消化及介入诊疗》2024年第5期560-564,共5页Modern Interventional Diagnosis and Treatment in Gastroenterology

基　　金：山西省医学重点科研项目(2023XM024)。

摘　　要：目的探讨恩沃利单抗对AGS胃癌细胞增殖、侵袭和迁移的影响及作用机制。方法体外培养AGS细胞,实验分为恩沃利单抗组(分别含有2.5、5、10、20、40 mg/mL恩沃利单抗的培养液)和对照组(同等体积的生理盐水)。细胞计数试剂盒8(CCK8)法检测细胞的活性,Transwell检测细胞的侵袭和迁移,流式检测细胞的凋亡。蛋白质组学检测分析两组差异蛋白和相关信号通路,蛋白印迹对发现的差异蛋白和通路进行验证。结果与对照组相比,恩沃利单抗组显著降低AGS细胞的存活率(P=0.0060);也能够显著抑制AGS细胞的侵袭和迁移细胞数(P=0.0052),并且可以促进AGS细胞的凋亡(P=0.0030)。聚类分析和京都基因与基因组百科全书(KEGG)富集发现,相比于对照组,恩沃利单抗组中溶质载体家族1成员3(SLC1A3)蛋白的表达显著下调,并与丝裂原活化蛋白激酶(MAPK)通路相关。蛋白印迹实验显示,加入了恩沃利单抗的AGS细胞中SLC1A3蛋白的表达明显降低(P=0.0041),丝裂原活化的细胞外信号调节激酶(MEK)和细胞外信号调节激酶(ERK)磷酸化的水平也显著降低(P=0.0008)。结论恩沃利单抗可能通过下调SLC1A3的表达,抑制ERK/MAPK信号通路,发挥抑制AGS胃癌细胞生长的作用。恩沃利单抗可能存在多个抗肿瘤作用机制。Objective To investigate the effect of envafolimab on the proliferation,invasion and migration of AGS gastric cancer cells and its mechanism.Methods AGS cells were cultured in vitro and divided into envafolimab groups(2.5,5,10,20 and 40mg/ml of envafolimab,respectively)and control group(equal volume of normal saline).Cell viability was detected by cell counting kit-8(CCK8)assay,cell invasion and migration were detected by Transwell assay,and cell apoptosis was detected by flow cytometry.The differential proteins and related signaling pathways of the two groups were analyzed by proteomics,and the differential proteins and pathways found were verified by Western blot.Results Compared with the control group,the survival rate of AGS cells was significantly decreased in the envafolimab group(P=0.0060).It also significantly inhibited the invasion and migration of AGS cells(P=0.0052),and promoted the apoptosis of AGS cells(P=0.0030).Cluster analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment revealed that solute carrier family 1 member 3(SLC1A3)protein expression was significantly down-regulated in the envafolimab group compared with the control group,which was related to the mitogen-activated protein kinase(MAPK)pathway.Western blot showed that the expression of SLC1A3 protein in AGS cells treated with envafolimab was significantly decreased(P=0.0041),and the phosphorylation levels of mitogen-activated extracellular signal-regulated kinase(MEK)and extracellular signal-regulated kinase(ERK)were also significantly decreased(P=0.0008).Conclusion Envafolimab can inhibit the growth of AGS gastric cancer cells possibly by down-regulating the expression of SLC1A3 and inhibiting the ERK/MAPK signaling pathway.Multiple antitumor mechanisms of action are possible for envafolimab.

关 键 词：恩沃利单抗 胃癌 SLC1A3 ERK MAPK 

分 类 号：R573[医药卫生—消化系统]