欧前胡素调节ThPOK表达对胃癌细胞恶性生物学行为的影响  

Effects of imperatorin on malignant biological behavior of gastric cancer cells by regulating ThPOK expression

作　　者：陈兰 夏伶俐 陈颖[1] 张刚 文峰 CHEN Lan;XIA Lingli;CHEN Ying;ZHANG Gang;WEN Feng(Dept.of Gastroenterology,Wuhan Sixth Hospital Affiliated to Jianghan University,Wuhan 430015,China;Dept.of Gastroenterology,Central Theater Command General Hospital,Wuhan 430012,China)

机构地区：[1]江汉大学附属武汉市第六医院消化内科,武汉430015 [2]中部战区总医院消化内科,武汉430012

出　　处：《中国药房》2025年第2期191-196,共6页China Pharmacy

基　　金：武汉市医学科研项目(No.WX20C29)。

摘　　要：目的 探究欧前胡素(IMP-SD)调节含锌指和BTB结构域7B(ThPOK)表达对胃癌(GC)细胞恶性生物学行为的影响。方法 取人GC细胞MKN-7,分为对照组(不给药),IMP-SD低、中、高浓度组(分别给予40、80、160μmol/L的IMP-SD),si-ThPOK和si-NC组[先给予160μmol/L的IMP-SD,再分别转染ThPOK小分子干扰RNA(si-ThPOK)及其阴性对照(si-NC)])。经相应处理后,检测各组细胞的克隆形成、迁移、侵袭能力及凋亡情况,自然杀伤(NK)细胞的杀伤作用,T细胞的分布情况,以及ThPOK、程序性死亡受体1(PD-1)及其配体(PD-L1)的表达情况。结果 与对照组比较,IMP-SD各浓度组的细胞克隆数、迁移细胞数、侵袭细胞数和PD-1、PD-L1蛋白的表达均显著降低或下调,细胞凋亡率、NK细胞的杀伤活性、CD4^(+)T细胞比例、CD4^(+)T细胞比例与CD8^(+)T细胞比例的比值(CD4^(+)T/CD8^(+)T)、ThPOK蛋白的表达均显著升高或上调,且有浓度依赖性(P<0.05);与IMP-SD高浓度组和siNC组比较,si-ThPOK组的细胞克隆数、迁移细胞数、侵袭细胞数和PD-L1、PD-1蛋白的表达均显著升高或上调,细胞凋亡率、NK细胞的杀伤活性、CD4^(+)T细胞比例、CD4^(+)T/CD8^(+)T、ThPOK蛋白的表达均显著降低或下调(P<0.05)。结论 IMP-SD可能通过促进ThPOK蛋白的表达,从而减弱GC细胞的克隆形成、迁移、侵袭能力,促进其凋亡,抑制其免疫逃逸。OBJECTIVE To investigate the effects of imperatorin(IMP-SD)on malignant biological behavior of gastric cancer(GC)cells by regulating zinc finger and BTB domain 7B(ThPOK).METHODS Human GC cells MKN-7 were used as the research object and then divided into control group(no treatment),IMP-SD low-,medium-and high-concentration groups(40,80 and 160μmol/L IMP-SD),si-ThPOK and si-NC group[treated with 160μmol/L IMP-SD and then transfected with ThPOK small interfering RNA(si-ThPOK)or its negative control(si-NC)].After treatment,cell clone formation,migration and invasion abilities and apoptosis of MKN-7 cells were detected;the killing activity of NK cells,T cells classification,the protein expressions of ThPOK,programmed death-1(PD-1)and programmed death-ligand 1(PD-L1)were all determined.RESULTS Compared with the control group,the number of cell clones,migration number,invasion number,and the protein expressions of PD-1 and PD-L1 were decreased or down-regulated significantly in IMP-SD groups,while the cell apoptotic rate,NK cell killing activity,CD4^(+)T proportion,the ratio of CD4^(+)T proportion and CD8^(+)T proportion(CD4^(+)T/CD8^(+)T),and the protein expression of ThPOK were increased or up-regulated significantly,in a concentration-dependent manner(P<0.05).Compared with IMP-SD high-concentration group and si-NC group,the number of cell clones,migration number,invasion number,and the protein expressions of PD-1 and PD-L1 were increased or up-regulated significantly in si-ThPOK group,while the cell apoptotic rate,NK cell killing activity,CD4^(+)T proportion,CD4^(+)T/CD8^(+)T,and the protein expression of ThPOK were decreased or down-regulated significantly(P<0.05).CONCLUSIONS IMP-SD may reduce the clonal formation,migration and invasion abilities of GC cells,promote their apoptosis and inhibit their immune escape by promoting ThPOK expression.

关 键 词：欧前胡素 ThPOK 胃癌细胞 免疫逃逸 恶性生物学行为 

分 类 号：R965[医药卫生—药理学] R735.2[医药卫生—药学]