盐酸双吗啡肽对耐药食管癌细胞迁移和侵袭能力的影响  

Effect of dorsomorphin on the migration and invasion abilities of drug-resistant esophageal cancer cells

作　　者：石晓丽 苏治国[1] 张英[1] 杨国帅[1] 彭温暖 王晨[1] 马霖[1] SHI Xiaoli;SU Zhiguo;ZHANG Ying;YANG Guoshuai;PENG Wennuan;WANG Chen;MA Lin(Department of Pharmacy,The Affiliated Hospital of Qingdao University,Qingdao 266700,China)

机构地区：[1]青岛大学附属医院药剂科,山东青岛266700

出　　处：《精准医学杂志》2024年第6期547-551,共5页Journal of Precision Medicine

摘　　要：目的 探讨骨形态发生蛋白(BMP)小分子抑制剂盐酸双吗啡肽(Dorsomorphin)对耐药食管癌EC109/PTX细胞迁移和侵袭能力的影响。方法 MTT实验检测不同浓度盐酸双吗啡肽对EC109/PTX细胞增殖的影响并确定后续实验的浓度。以筛选出的1μmol/L盐酸双吗啡肽的浓度作为试验组,同时设立空白对照组,处理EC109/PTX细胞48 h。采用流式细胞仪检测盐酸双吗啡肽对EC109/PTX细胞凋亡的影响。采用划痕实验和Transwell实验检测两组EC109/PTX细胞的迁移和侵袭能力。采用Western blotting实验检测两组EC109/PTX细胞中Vimentin、E-cadherin、N-cadherin蛋白相对表达水平。结果 1μmol/L盐酸双吗啡肽对EC109/PTX细胞的细胞抑制率为(9.89±1.12)%。培养第48小时时,对照组和实验组EC109/PTX细胞的凋亡率比较差异无显著性(P>0.05)。划痕实验和Transwell实验显示,与对照组相比,实验组EC109/PTX细胞的迁移率和细胞穿膜率显著降低(t=85.42、19.65,P<0.05)。Western blotting实验显示,与对照组相比,实验组细胞中Vimentin、N-cadherin蛋白相对表达量显著降低(t=19.40、41.79,P<0.05),N-cadherin蛋白表达量显著增高(t=58.12,P<0.05)。结论 BMP抑制剂盐酸双吗啡肽能影响耐药食管癌细胞中EMT相关蛋白表达,从而抑制耐药肿瘤细胞的迁移和侵袭。Objective To investigate the effect of dorsomorphin,a bone morphogenetic protein(BMP)small-molecule inhibitor,on the migration and invasion abilities of drug-resistant esophageal cancer EC109/PTX cells.Methods MTT assay was used to observe the effect of different concentrations of dorsomorphin on the proliferation of EC109/PTX cells and determine the concentration for subsequent experiments.Dorsomorphin at the concentration of 1μmol/L was established as the experimental group,and a blank control group was set up.EC109/PTX cells were treated for 48 h.Flow cytometry was used to observe the effect of dorsomorphin on the apoptosis of EC109/PTX cells;scratch assay and Transwell assay were used to observe the migration and invasion abilities of EC109/PTX cells;Western blotting was used to measure the relative protein expression levels of Vimentin,E-cadherin,and N-cadherin in EC109/PTX cells.Results Dorsomorphin at the concentration of 1μmol/L showed an inhibition rate of(9.89±1.12)%on the proliferation of EC109/PTX cells.At 48 h of culture,there was no significant difference in the apoptosis rate of EC109/PTX cells between the control group and the experimental group(P>0.05).Scratch assay and Transwell assay showed that compared with the control group,the experimental group had significant reductions in the migration rate and cell permeation rate of EC109/PTX cells(t=85.42,19.65,P<0.05).Western blotting showed that compared with the control group,the experimental group had significant reductions in the relative protein expression levels of Vimentin and N-cadherin(t=19.40,41.79,P<0.05)and a significant increase in the protein expression level of N-cadherin(t=58.12,P<0.05).Conclusion The BMP inhibitor dorsomorphin can inhibit the migration and invasion abilities of drug-resistant tumor cells by affecting the expression of epithelial-mesenchymal transition-related proteins in drug-resistant esophageal cancer cells.

关 键 词：骨形态发生蛋白质4 Dorsomorphin 抗药性 肿瘤 食管肿瘤 细胞运动 肿瘤浸润 上皮-间质转化 基因表达调控 肿瘤 

分 类 号：R735.1[医药卫生—肿瘤] R394[医药卫生—临床医学]