Research On Candidate Compounds And The Effects For Improving The Sensitivity Of TRAIL Based On Bioinformatics In NSCLC

Objectives:Tumor necrosis factor related apoptosis inducing ligand（TRAIL）also known as APO-2L,is a inducing factor of tumor cell apoptosis.TRAIL can selectively kills multiple tumor cells without affecting normal cells.Therefore,it has developed into a new antitumor drug.However,clinical data suggest that,a number of patients have resistance to TRAIL treatment,which includes Non-Small Cell Lung Cancer（NSCLC）.Therefore,the discovery and screening of drugs that can enhance the therapeutic effect of TRAIL or increase the sensitivity of cancer cells to TRAIL is very urgent.This study excavates candidate drugs that may enhance the effect of TRAIL through bioinformatics analysis,hoping to provide a new strategy to enhance the sensitivity of NSCLC to TRAIL,and to provide some references for the promotion,transformation and combined treatment of subsequent TRAIL in clinical application.Methods:Through prior bioinformatics and database analysis,the expression profiles of TRAIL-resistant and TRAIL-sensitive H460 cells were retrieved in the GEO database.And then use differential genes for c MAP analysis,some candidate drugs that may reverse TRAIL resistance was obtained.Cell Counting Kit-8（CCK-8）,DAPI staining,Western blotting,Flow cytometry and other experimental methods are used to explore whether candidates have the ability to improve TRAIL antitumor activity and its potential molecular mechanism.Results:Through preliminary bioinformatics and database analysis,resistance mechanism of TRAIL was explored and screening.Experiments showed that TPCA-1improved TRAIL sensitivity in both NCI-H460 and A549,and further found that sensitization of TPCA-1 on TRAIL may be achieved by inhibiting cell migration and promoting apoptosis.Literature research found that a series of downstream targets of NF-κB,one of TPCA-1 targets,may be related to TRAIL resistance progress,we initially investigate the relevant molecular mechanism of sensitization effect of TPCA-1on TRAIL and show that TPCA-1 may sensitize DR5 expression and inhibite the expression of survivin,c-IAP2.Conclusion: In conclusion,this study verified the sensitization effect of TPCA-1on TRAIL based on bioinformatics analysis and we further validate sensitization effects of TPCA-1 on TRAIL and initially explore the relevant molecular mechanisms.This paper provides new strategies for improving the sensitivity of TRAIL therapy in NSCLC,hoping to provide some reference for the advancement,transformation and combined treatment of TRAIL in clinical applications.