SB743921通过靶向调控衰老相关基因TRAP1对结肠癌细胞HCT116迁移的影响OA

Aim:To explore the role of the senescence-related gene TRAP1 in the migration of colon cancer cell HCT116 and screen for its potential targeted drug molecules.Methods:Transcriptomic data from 462 colon cancer tissues and 41 adjacent normal tissues in the TCGA database,together with the GSE14297 dataset from the GEO database,were in-tegrated.WGC NA was used to screen senescence-related genes based on the CellAge database.An TRAP1-knockdown HCT116 cell model was established and Western blot was performed to detect TRAP1 protein expression.Transcriptome se-quencing was used to identify differentially expressed genes,followed by KEGG pathway enrichment analysis.Based on the GDSC2 and CTRP drug sensitivity databases,oncoPredict was used to analyze the association between TRAP1 expression and drug sensitivity,and molecular docking was performed to screen potential drugs binding to TRAP1.Cell viability was as-sessed using the CCK-8 proliferation assay in HCT116 cells treated with 0.00,0.10,0.25,0.40,0.50 nmol/L SB743921 for 24 hours.HCT116 cells were divided into SB743921 treated group(exposed to 0.50 nmol/L SB743921)and DMSO group(exposed to equal volume of DMSO).Cell migration was evaluated by wound healing assay,and the migration distance was measured at 24 and 48 hours post wounding.Additionally,the mRNA expression levels of TRAP1,matrix metalloprotein-ase-2(MMP-2),and fibronectin 1(FN1)were detected using RT-qPCR.Results:A total of 46 senescence-related genes associated with colon cancer development and liver metastasis were identified,including 42 upregulated and 4 downregulated genes.WGCNA further identified 9 candidate genes,including TRAP1.The TRAP 1-knockdown cells showed lower TRAP1 protein expression,and the migration distances at 24,48,and 72 hours were also smaller(P＜0.05).The differentially ex-pressed genes were mainly enriched in pathways related to cellular senescence.SB743921 had a high binding affinity for TRAP1,with a binding energy of-33.26 kJ/mol.After treatment with 0.25,0.40,0.50 nmol/L SB743921 HCT116 cell viability decreased(P＜0.05).Compared with DMSO group,the migration distances at 24 and 48 hours reduced,and the mRNA expression levels of TRAP1,MMP-2,and FN1 also decreased in SB743921 treated group(P＜0.05).Conclusion:SB743921 may inhibit colon cancer cell HCT116 migration by binding to the senescence-related protein TRAP1.