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

doi:10.3969/j.issn.1004-616x.2025.03.001

Abstract

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.

Key words: GNE-7883, esophageal squamous cell carcinoma, proliferation, migration, apoptosis

CLC Number:

R735.1

LU Xiaotong, SHI Jianhong, XIAO Xue, CHEN Siqi, HAO Jiajie, CAI Yan, WANG Mingrong, ZHANG Yu. Involvement of transcriptional enhanced associate domain inhibitor GNE-7883 on malignant phenotypes in esophageal squamous cell carcinoma[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(3): 177-182.

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Involvement of transcriptional enhanced associate domain inhibitor GNE-7883 on malignant phenotypes in esophageal squamous cell carcinoma

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