硫利达嗪抗宫颈癌的潜在作用机制  

Potential Mechanism of Thioridazine in Anti-cervical Cancer

作　　者：谢芹 赵春阳 张葆溯 赵洪波[1] XIE Qin;ZHAO Chunyang;ZHANG Baosu;ZHAO Hongbo(Institute of Biomedical Engineering&Yunnan Key Laboratory of Stem Cell and Regenerative Medicine Kunming Medical University,Kunming Yunnan 650500,China)

机构地区：[1]昆明医科大学生物医学工程研究院暨云南省干细胞和再生医学重点实验室,云南昆明650500

出　　处：《昆明医科大学学报》2022年第3期13-20,共8页Journal of Kunming Medical University

基　　金：云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目(202101AY070001-075);云南省教育厅科学研究基金资助项目(2021J0226)。

摘　　要：目的运用生物信息学分析,探讨硫利达嗪抗宫颈癌的潜在作用机制。方法通过PharmMapper工具预测能够与硫利达嗪相互作用的靶基因,然后使用STRING在线工具对靶基因进行通路和组织表达富集分析。使用GeneCards和DisGeNET数据库筛选宫颈癌相关基因,与硫利达嗪的靶基因取交集,得到硫利达嗪可能作用于宫颈癌的交互基因。通过STRING构建蛋白互作(PPI)网络,推测核心靶点,评估其重要性。使用clusterProfiler软件进行GO和KEGG通路分析。结果通过PharmMapper预测得到47个靶基因,富集到肿瘤相关通路和宫颈癌细胞。与669个宫颈癌基因取交集,获得硫利达嗪和宫颈癌交互基因21个,其中10个关键节点基因为EGFR、PPARG、AR、NOS3、ALB、ESR1、MAPK1、MAPK14、ANXA5和MAPK8,且在宫颈癌PPI网络中处于重要位置。交互基因涉及到的生物进程主要有负离子转运的正调控、丝氨酸肽基磷酸化、类固醇代谢过程、血液凝固、细胞对化学应激的反应等。富集的KEGG通路包括调控癌症通路、松弛素信号通路、内分泌耐药、蛋白聚糖与肿瘤、细胞衰老、GnRH信号通路和VEGF信号通路等。结论硫利达嗪具有潜在的抗肿瘤作用,可能通过多靶点和多信号通路的方式在宫颈癌的治疗上发挥作用。Objective To explore the potential mechanism of thioridazine in the treatment of cervical cancer by bioinformatics analysis.Methods The target genes that can interact with thioridazine was predicted by PharmMapper,and then conducted pathway and tissue expression enrichment analysis by STRING online tool.The cervical cancer related genes were screened through GeneCards and DisGeNET databases,and cross the target genes of thioridazine to obtain the interaction genes that thioridazine may act on cervical cancer.The protein-protein interaction(PPI)network was constructed using STRING,and the core targets were speculated and evaluated their importance.The GO and KEGG enrichment analysis were conducted using clusterProfiler package.Results A total of 47 target genes were predicted by PharmMapper,which were enriched in tumor-related pathways and cervical cancer cells.Intersection with 669 cervical cancer genes,21 common genes were obtained,of which 10 key genes were EGFR,PPARG,AR,NOS3,ALB,ESR1,MAPK1,MAPK14,ANXA5 and MAPK8.These key genes were important in the cervical cancer PPI network.The biological processes involved in interactive genes mainly include positive regulation of anion transport,peptidyl-serine phosphorylation,steroid metabolic process,blood coagulation,and cellular response to chemical stress.Enriched KEGG pathways include pathways in cancer,relaxin signaling pathway,endocrine resistance,proteoglycans in cancer,cellular senescence,GnRH signaling pathway,and VEGF signaling pathway.Conclusion Thioridazine has potential anti-tumor effects and may play a role in the treatment of cervical cancer through multiple targets and multiple signaling pathways.

关 键 词：硫利达嗪 宫颈癌 靶点 作用机制 

分 类 号：R737.3[医药卫生—肿瘤]