中国肿瘤生物治疗杂志2026，Vol.33Issue(8)：867-875,9.DOI:10.3872/j.issn.1007-385X.2026.08.007
基于蛋白质组学与分子模拟探讨COX17参与去甲泽拉木醛抑制胃癌MGC-803细胞增殖和侵袭的作用机制
Proteomics and molecular simulation analyses of COX17 involvement in demethylzeylasteral-mediated inhibition of proliferation and invasion of MGC-803 gastric cancer cells
摘要
Abstract
Objective:To investigate whether cytochrome c oxidase copper chaperone 17(COX17)is involved in the inhibitory effects of demethylzeylasteral(DML)on the proliferation and invasion of gastric cancer cells.Methods:MGC-803 cells were treated with DML at 5,10 and 20 μmol/L,and the effects of DML on cell proliferation and invasion were evaluated by manual cell counting and Transwell assay,respectively.Label-free quantitative proteomics was applied to compare the protein expression profiles between the DML-treated group and the DMSO group,and candidate proteins were screened by differential expression analysis combined with Gene Ontology(GO)functional enrichment analysis.The change in COX17 protein expression after DML treatment was verified by Western blotting.COX17-knockdown and COX17-overexpressing stable cell lines were constructed separately,and the effects of COX17 on the proliferation and invasion of MGC-803 cells were evaluated by cell counting and Transwell assay.Molecular docking and 50 ns molecular dynamics simulation were used to analyze the potential binding mode between DML and COX17 as well as the conformational stability of the complex.The role of COX17 in the DML-induced inhibition of cell proliferation and invasion was further evaluated by a COX17 overexpression rescue experiment.Results:DML significantly inhibited the proliferation and invasion of MGC-803 cells,and the inhibitory effect was progressively enhanced with increasing DML concentration(all P<0.000 1).A total of 72 differentially expressed proteins were screened by proteomics,of which 21 were upregulated and 51 were downregulated.Based on these differential expression characteristics,the GO enrichment results and our previous findings,COX17 was selected for further validation.DML significantly downregulated COX17 protein expression in MGC-803 cells(P<0.000 1).Knockdown of COX17 inhibited cell proliferation and invasion,whereas overexpression of COX17 promoted these malignant phenotypes.Molecular docking suggested that interactions such as hydrophobic contacts,hydrogen bonds and salt bridges might exist between DML and COX17,with a docking score of-6.8 kcal/mol.Molecular dynamics simulation showed that the DML-COX17 complex tended to be relatively stable overall during the 50 ns simulation.Overexpression of COX17 partially attenuated the inhibitory effects of DML on the proliferation and invasion of MGC-803 cells(P<0.01).Conclusion:DML can inhibit the proliferation and invasion of MGC-803 cells and downregulate COX17 protein expression,and COX17 may be involved in the regulation of the malignant phenotypes of gastric cancer cells by DML.关键词
去甲泽拉木醛/细胞色素c氧化酶铜伴侣蛋白17/胃癌/蛋白质组学/分子动力学模拟Key words
demethylzeylasteral(DML)/cytochrome c oxidase copper chaperone 17(COX17)/gastric cancer/proteomics/molecular dynamics simulation分类
医药卫生引用本文复制引用
杨丹,熊心芽,廖聪慧,陈洁,孙杭杭,韩然..基于蛋白质组学与分子模拟探讨COX17参与去甲泽拉木醛抑制胃癌MGC-803细胞增殖和侵袭的作用机制[J].中国肿瘤生物治疗杂志,2026,33(8):867-875,9.基金项目
贵州省高层次创新型人才"千层次"人才培养项目(GZSYQCC[2020]009) （GZSYQCC[2020]009）
