基于含硒衍生物在癌症治疗中发挥的重大作用，文中以前期合成的2-(2-苯氨甲酰基甲硫基-1，3，4-噻二唑-5-基)-1，2-苯并异硒唑3(2H)-酮化合物(2-(2-phenylaminomethylthio-1，3，4-thiadiazol-5-yl-1，2-benziselenazol-3(2H)-one compound，PTBO)为受试药，通过体外细胞培养，结合转录组测序方法，考察该衍生物对人乳腺癌细胞(michigan cancer foundation-7，MCF-7)的基因表达的影响，分析基因表达的差异，以期为该含PTB0对肿瘤细胞的抑制作用机制的研究提供参考。结果证明，与未经处理的MCF-7细胞相比，PTBO引起基因差异表达2 561个，其中差异表达基因上调1 744个，差异表达基因下调817个。通过GO(geneontology)功能富集和KEGG(kyoto encyclopedia of genes and genomes)通路分析发现，PTBO会导致蛋白质分解、蛋白质的衰变等相关基因的差异表达;通过下调包括周期蛋白依赖性激酶4和6(cyclin-dependent kinase 4/6，CDK4/CDK6)等基因表达，PTBO可以调控P53信号通路和肿瘤坏死因子(tumour necrotizing factor，TNF)信号通路，并显著上调了抑癌基因(P53)、细胞周期抑制基因(P21)和死亡结构域蛋白(fas associated via death domain，FADD)的表达，从而阻止细胞周期、导致肿瘤细胞凋亡。
Effect of a selenium derivative PTBO on breast cancer MCF-7 cells and its transcriptomics analysis
Based on the significant role played by selenium-containing derivatives in cancer therapy.In thisthesis,2-(2-phenylaminomethylthio-1,3,4-thiadiazol-5-yl)-1,2-benziselenazol-3(2H)-one compound(PTBO)was synthesized as the test drug in a previous stage,and the effect of this derivative on the gene expression of MCF-7cells was investigated by vitro cell culture combined with transcriptome sequencing method to analyze the difference of gene expression,in order to provide a reference for this PTBO-containing.The results demonstrated that the effect of the derivative on the gene expression of MCF7 cells was different from that of untreated MCF-7cells.It was found that PTBO caused 2 561 differentially expressed genes,including 1 744 up-regulated differentially expressed genes and 817 down-regulated differentially expressed genes,compared with untreated MCF-7 cells.Next,the differentially expressed genes were analyzed by GO functional enrichment and KEGG pathway analysis.It was found that PTBO could cause differential expression of genes related to proteolysis and protein decay.Specifically,the expression of cyclin-dependent kinase 4 and 6(CDK4/CDK6)genes was downregulated byregulating P53 signaling pathway and TNF signaling pathway.and its related genes,and the expression of P53,cellcycle inhibitor gene(P21)and fas associated via death domain(FADD)was significantly upregulated to stop cell cycle and cause apoptosis of tumor cells.
selenium derivativesbreast cancer cellstranscriptome sequencing technologydifferentially expressed genescell apoptosis
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