To Investigate The Effect Of Cinnamaldehyde On Apoptosis And Protein Expression In Cervical Carcinoma Cells Based On Bioinformatics

Objective:（1）To identify biomarkers in cervical cancer patient samples by multiple bioinformatics tools.（2）To investigate the effects of cinnamaldehyde（CA）on the proliferation,migration,and apoptosis of cervical cancer cells and analyze its molecular mechanism.Methods:（1）Three data sets of cervical cancer were obtained by GEO.Differentially expressed genes（DEGs）were obtained by R software analysis and enriched.Protein-protein interaction（PPI）networks were built using the STRING database and hub genes were identified by visual analysis in Cytoscape.Studies were further analyzed using UALCAN,c Bio Portal,and the Human Protein Atlas（HPA）database.（2）CCK-8 was used to determine the IC₅₀ value of CA on cervical cancer cells and the synergy index after combined administration with Tax,Pt,and 5-FU;scratch assay was used to detect the effect of CA on cervical cancer cell migration;flow cytometry was used to detect the effect of CA on cervical cancer cell cycle;Hoechst 33342 fluorescence staining and Western blot were used to detect the effect of CA on cervical cancer cell apoptosis;JC-1 fluorescence probe was used to detect the change of mitochondrial membrane potential in cervical cancer cells;Western blot was used to detect the effect of CA on cervical cancer cells through proteasome pathway and the expression of related proteins.Results:（1）257 DEGs were obtained by R software analysis.KEGG and GO enrichment analysis showed that they were mainly enriched in the cell cycle,apoptosis,and DNA replication process.Four hub genes（AURKB,CDK1,KIF11,and KIF2C）were obtained based on MCODE and cyto Hubba plug-in analysis,and these four genes were highly expressed in cervical cancer tissues by analysis using UALCAN,c Bio Portal,and HPA databases.（2）CA inhibited the proliferation and migration of cervical cancer cells;arrested in the G2/M phase;disrupted mitochondrial membrane potential;inhibited the expression of E6/E7 protein and induced apoptosis through the proteasome pathway.It was further verified that cinnamaldehyde had synergistic anti-cervical cancer effects with chemotherapeutic agents Tax,Pt,and 5-FU.Conclusion:（1）The potential hub gene of carcinogenesis and progression of cervical cancer may be a novel biomarker for the diagnosis and treatment of cervical cancer.（2）CA induced apoptosis in Siha cells through the mitochondrial pathway and down-regulated the expression of HPV E6/E7 protein through the proteasome pathway;at the same time,it showed a synergistic effect at the cellular level with a variety of commonly used chemotherapeutic drugs for cervical cancer.