| Objective:In this paper,we studied the mechanism of Brucea javanica on ovarian cancer cells in vitro from bioinformatics(network pharmacology and gene chip)analysis.Methods:1.To verify the effect of Brucea javanica on ovarian cancer:(1)different concentrations of Brucea javanica oil emulsion injection were used acted on human ovarian cancer SKOV3 and SKOV3/Taxol-25 cells to confirm the IC50 value and non-toxic concentration of Brucea javanica oil emulsion injection and test the non-toxic concentrations of Brucea javanica oil emulsion injection and taxol injection by CCK-8.20ug/ml)combined with inhibitory effect on human ovarian cancer cells.(2)qRT-PCR was used to detect the mRNA expression of MDR/ABCB1 in different groups.2.The effective components and potential mechanism of Brucea javanica were studied by network pharmacology: the effective components of Brucea javanica were screened from the TCMSP platform,TargetNet targets predict the possible targets of Brucea javanica.DRUGBANK,OMIM and other databases are used to mine targets related to the occurrence and development of ovarian cancer,gene ontology and KEGG were enriched and analyzed,and finally the network relationship between component,target and pathway was constructed by Cytoscape3.6.0 software3.gene chip analysis: SKOV3/Taxol-25 cells(blank group,taxol group and combined drug group)were detected by gene chip,and analyse the different expressed genes use GO and KEGG.Results:1.Brucea javanica oil emulsion injection could inhibit the survival rate of human ovarian cancer SKOV3 and SKOV3/Taxol-25 cells,and the inhibitory effect was positively correlated with the concentration of Brucea javanica oil emulsion injection.The combination of acellular Brucea javanica oil injection and taxol injection could enhance the inhibitory effect of taxol,and the acellular concentration of Brucea javanica oil emulsion injection could decrease the expression of ABCB1 gene in SKOV3/Taxol-25 cells.2.Results of online pharmacology: the active components of Brucea javanica were lipidOlein and luteolin.The predicted targets were matched with 13 target proteins of ovarian cancer target,which might be mediated by biological effects such as drug response and signaling pathways(e.g.viral carcinogenic,Pathways in cancer),the signaling pathway of cancer,acts on ovarian cancer.3.The results of gene chip showed that the differentially expressed genes were screened by up-regulating or down-regulating(Fold change)≥ 2 times,and P < 0.05 as the screening criterion.There were 174 significantly different genes between BT group and taxol group,12 genes up and162 genes were down.Brucea javanica oil emulsion injection is regulated by changing the expression of differentially expressed genes biological processes(such as Cell-Cell adhesion 、response to drug)and signal pathways like Adipocytokine signaling pathway.Conclusion:The results showed that:(1)Brucea javanica could inhibit the proliferation of ovarian cancer cells and reduce the resistance of ovarian cancer cells to taxol.The main active components are oil and rhinocerol.(2)the combination of acellular Brucea javanica oil emulsion injection and taxol injection has a better inhibitory effect on the proliferation of SKOV3/Taxol-25 cells and changes genes.The expression of taxol can inhibit taxol resistance by regulating the biological functions and signaling pathways of ovarian cancer cells. |
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