Bioinformatics-based approaches for the molecular mechanisms of the antitumour effects of atorvastatin

doi:10.3969/.issn.1674-3245.2017.04.002

Abstract：Objective To discover the molecular mechanism and the pathway of the anti-carcinoma effect of atorvastatin based on bioinformatics. Methods The human umbilical vein endothelial cell line EA.hy 926 was divided into two groups. The experimental group was incubated with atorvastatin (10-5 mol/L) in vitro for 24 h, and the control group was incubated with DMSO (0.01%). Total RNA from these cells was extracted and analysed for gene expression profiling. SAM microarray analysis software was used to analyse the different genes between the control and experiment groups. Gene set enrichment analysis (GSEA) and DAVID were used for gene ontology(GO) and the pathway analysis. A connectivity map(Cmap) was used to analyse the different genes. RT-PCR and Westernblot analysis were used to verify the target genes related to tumour signalling pathways. Results Compared with the control group,649 genes were detected with marked changes in the experimental group,with 295 up-regulated genes and 354 down-regulated genes in atorvastatin-treated EA.hy 926 cells. Kruppel groups in up-regulated gene expression and cell cycle genes including CCNA2,CCNE2,CCNB1 and CCNB2 in down-regulated gene expression changed with statistical significance according to GSEA and were also verified by real-time PCR. In the Cmap analysis, the profiles of the HDAC inhibitor MS-275 ,trichostatin A and resveratrol were found to be highly similar to that of atorvastatin. Conclusion Based on the bioinformatics,atorvastatin has a synergistic effect with histone deacetylase inhibitors,resveratrol and phenothiazine derivatives. Atorvastatin plays a similar role to histone deacetylase inhibitors and the cell cycle inhibitors of the G1/S phase (start) and the G2/M (mitosis) phase. These findings demonstrate the feasibility of atorvastatin as an antitumour drug.