生脉胶囊逆转小鼠结肠癌细胞5-氟尿嘧啶耐药研究OACSTPCD

[Objective]To explore the effect and mechanism of Shengmai capsule(SM)on reversing 5-fluorouracil(5-FU)resistance in mouse colon cancer cells.[Methods]Target genes regulated by SM(gene set 1)were obtained from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine.Chemotherapy resistance related genes(gene set 2)and 5-FU resistance related genes(gene set 3)were both retrieved from Gene Cards database.The intersection of three gene sets was used for subsequent analysis.The Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed.5-FU resistant CT26 cells(CT26/FU)were obtained and used to construct mouse xenograft model.The tumor-bearing mice were than divided into model group,FU group(intraperitoneal injection of 5-FU)and FU+SM group(intraperitoneal injection of 5-FU and gavage with SM).The size of xenografts was measured every day and the mice were sacrificed 10 days later while the xenografts were weighted.Total RNA of xenografts was extracted and Realtime RT-PCR was performed to detect the expression of 5-FU resistance related genes thymidylate synthase(TYMS),dihydropyrimidine dehydrogenase(DPYD),DNA topoisomerase Ⅱ(TOP2A),nicotinamide-N-methyltransferase(NNMT)and glucocorticoid receptor(nuclear receptor subfamily 3 group C member 1,NR3C1).[Results]The 38 candidate genes were screened with network pharmacology analysis and these genes were enriched in multiple drug resistance pathways.Animal experiments suggested that there was no difference in tumor size and weight between the FU group and the model group.However,the size and weight of xenografts were decreased in the FU+SM group.Meanwhile,compared with the FU group,the expression of TOP2A in the FU+SM group decreased.[Conclusion]SM can reverse the drug resistance of CT26/FU,and its mechanism may be related to downregulating the expression of TOP2A.