天津中医药2024，Vol.41Issue(7)：898-903,6.DOI:10.11656/j.issn.1672-1519.2024.07.17
生脉胶囊逆转小鼠结肠癌细胞5-氟尿嘧啶耐药研究
Reversal effect of Shengmai capsule on 5-fluorouracil resistance in mouse colon cancer cells
摘要
Abstract
[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.关键词
生脉胶囊/结肠癌/5-氟尿嘧啶/化疗耐药/DNA拓扑异构酶Ⅱ αKey words
Shengmai capsule/colon cancer/5-fluorouracil/chemoresistance/DNA topoisomerase Ⅱ α分类
临床医学引用本文复制引用
阎皓,彭雁飞,于小惠,冯丹丹,赵玉萌,喻嫄嫄,李兆栋,巩祖妍,王晨曦,赵舒武..生脉胶囊逆转小鼠结肠癌细胞5-氟尿嘧啶耐药研究[J].天津中医药,2024,41(7):898-903,6.基金项目
天津市自然科学基金多元投入基金资助项目(21JCYBJC01830) （21JCYBJC01830）
2022结直肠癌和头颈肿瘤医学种子科研基金(2019BQEYH). （2019BQEYH）
