癌变·畸变·突变2025，Vol.37Issue(3)：177-182,6.DOI:10.3969/j.issn.1004-616x.2025.03.001
转录增强相关结构域抑制剂GNE-7883对食管鳞癌细胞恶性表型的影响及其分子机制
Involvement of transcriptional enhanced associate domain inhibitor GNE-7883 on malignant phenotypes in esophageal squamous cell carcinoma
摘要
Abstract
OBJECTIVE:To investigate effects of the Yes-associated protein-transcriptional enhanced associate domain(YAP-TEAD)small-molecule inhibitor GNE-7883 on malignant phenotypes and molecular mechanisms in esophageal squamous cell carcinoma(ESCC)cells.METHODS:KYSE410 and KYSE510 cells were treated with varying concentrations of GNE-7883(8,16,50,and 100 μmol/L)for 24 or 48 hours,with DMSO as control.Cell proliferation,colony formation,migration,and apoptosis were assessed.Molecular expression changes were analyzed by qPCR and Western blot.RESULTS:Compared to controls,50 and 100 μmol/L of GNE-7883 significantly inhibited proliferation and colony formation in both cell lines(P<0.01),and induced apoptosis under serum-free conditions(P<0.05).Under serum-free conditions,8 and 16 μmol/L of GNE-7883 significantly inhibited cell migration(P<0.01).Normal cultures treated with 50 and 100 μmol/L of GNE-7883 reduced CTGF,CYR61,c-Myc,p-ERK and p-AKT levels.Serum-free conditions with 50 and 100 μmol/L of GNE-7883 increased Cleaved PARP and Cleaved Caspase-3,while decreasd CTGF,CYR61,Bcl-2,Bcl-xL,c-Myc,p-ERK and p-AKT.Serum-free conditions with 8 and 16 μmol/L of GNE-7883 down-regulated CTGF,CYR61,MMP14,and p-ERK.CONCLUSION:GNE-7883 significantly suppressed proliferation,migration,and survival of esophageal squamous cell carcinoma(ESCC)cells and markedly inhibited activities of the MAPK/ERK and AKT/mTOR signaling pathways.It could be useful as a therapeutic candidate for ESCC.关键词
GNE-7883/食管鳞癌/增殖能力/迁移能力/细胞凋亡Key words
GNE-7883/esophageal squamous cell carcinoma/proliferation/migration/apoptosis分类
临床医学引用本文复制引用
卢晓童,史建红,肖雪,陈思琦,郝佳洁,蔡岩,王明荣,张钰..转录增强相关结构域抑制剂GNE-7883对食管鳞癌细胞恶性表型的影响及其分子机制[J].癌变·畸变·突变,2025,37(3):177-182,6.基金项目
国家自然科学基金(81872279) （81872279）
