马法兰治疗视网膜母细胞瘤作用机制初步研究

Mechanism of melphalan in the treatment of retinoblastoma

目的探究马法兰治疗视网膜母细胞瘤的分子生物学机制。方法实验研究。用马法兰处理不同时间点(4 h,8 h,12 h及24 h)的视网膜母细胞细胞系,进行mRNA-测序检测,通过GO和KEGG富集分析等生物信息学分析方法,探索马法兰治疗视网膜母细胞瘤中作用机制。结果生物信息学分析结果显示,视网膜母细胞瘤细胞接受马法兰处理后,基因表达谱产生了显著性变化。马法兰对基因表达影响最显著的作用时间为前4 h,共计1723个基因发生差异性表达。差异性表达基因主要涉及同源重组、DNA复制、剪接体、核糖体生物发生和脂代谢磷酸肌醇代谢等通路。结论马法兰可能通过抑制DNA复制和同源重组,并促进磷酸肌醇代谢和萜类化合物生物合成,达到抑制视网膜母细胞瘤生长并杀伤肿瘤细胞的作用。

Objective To investigate the underlying mechanism of melphalan in the treatment of retinoblastoma.Methods Experimental study.Retinoblastoma cell lines were treated with melphalan at 4 h,8 h,12 h and 24 h followed by mRNA-seq.The differentially expressed genes(DEGs)were analyzed with bioinformatics methods,including Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG).Results After administration of melphalan,RNA-seq showed that the gene-expression profile was changed and the most significant effect time was the first 4h.A total of 1723 genes were upregulated or downregulated,which were mainly involved in the homologous recombination,DNA replication,spliceosome,ribosome biological occurrence and lipid metabolism phosphoinositide metabolic.Conclusions Melphalan may play killing effect on retinoblastoma by inhibiting DNA replication and homologous recombination,and promoting the metabolism of phosphoinositide and terpenoid backbone biosynthesis.