改良增生平抑制口腔鳞状细胞癌的网络药理学研究及实验验证
Network pharmacology study and experimental verification of the inhibition of oral squamous cell carcinoma by modified Zeng-Sheng-Ping
王嘉祺 1林菲然 1杨森 2周永香 2关晓兵1
作者信息
- 1. 100050,首都医科大学附属北京口腔医院口腔黏膜科;100050,首都医科大学口腔医学院
- 2. 100050,首都医科大学口腔医学院
- 折叠
摘要
目的 探究改良增生平(Modified Zeng-Sheng-Ping,ZSP-M)抑制口腔鳞状细胞癌(Oral Squamous Cell Carcinoma,OSCC)的作用机制.方法 利用网络药理学分析获得ZSP-M与OSCC的交集靶点,进行GO和KEGG富集分析;通过细胞实验研究ZSP-M对OSCC细胞增殖、克隆形成、迁移、侵袭、凋亡等生物学行为的影响,Western blot验证相关靶点蛋白的表达.结果 ZSP-M与OSCC交集靶点168个,在肿瘤和炎症-免疫相关通路富集;ZSP-M呈剂量依赖性抑制SCC7和CAL27细胞克隆形成、迁移和侵袭,促进凋亡和Caspase-3酶释放,对增殖抑制作用不明显;ZSP-M呈剂量依赖性抑制SCC7和CAL27细胞AKT、ERK1/2和P65蛋白的磷酸化.结论 ZSP-M对OSCC的抑制作用呈现多靶点、多途径的特点,本研究为中西医结合防治口腔癌提供了科学依据.
Abstract
Objective Oral Squamous Cell Carcinoma(OSCC)is the most prevalent malignant tumor of the head and neck,posing a significant threat to patients'health.Zeng-Sheng-Ping,a traditional Chinese medicine,was previously utilized as an active anticancer agent with notable clinical efficacy,however,its administration was gradually discontinued due to hepatotoxicity.Our research group has developed Modified Zeng-Sheng-Ping(ZSP-M),which exhibits high efficiency and low toxicity in early-stage treatment.Nevertheless,the underlying pharmacodynamic mechanism remains unclear.The objective of this study was to investigate the pharmacodynamic mechanism of ZSP-M in inhibiting OSCC.Methods The intersection targets of ZSP-M and OSCC were obtained through network pharmacological analysis,and GO and KEGG enrichment analysis were performed.The effects of ZSP-M on OSCC cell proliferation,clonogenesis,migration,invasion,apoptosis and other biological behaviors were investigated through cell experiments.Western blot was performed to verify the expression of related target proteins.Results There were 168 intersection targets of ZSP-M and OSCC,which were enriched in tumor and inflammatory immune-related pathways.ZSP-M exhibited a dose-dependent inhibition on the formation,migration,and invasion of SCC7 and CAL27 cells.It also promoted apoptosis and Caspase-3 enzyme release without significantly affecting proliferation.Furthermore,ZSP-M inhibited the phosphorylation of AKT,ERK1/2,and P65 proteins in a dose-dependent manner in SCC7 and CAL27 cells.Conclusion The inhibitory effect of ZSP-M on OSCC demonstrates its characteristics as a multi-target agent acting through multiple pathways.This study provides scientific evidence for combining traditional Chinese medicine with Western medicine for the prevention and treatment of oral cancer.
关键词
口腔鳞状细胞癌/改良增生平/网络药理学/凋亡Key words
Oral squamous cell carcinoma/Modified Zeng-Sheng-Ping/Network pharmacology/Apoptosis引用本文复制引用
基金项目
北京市自然科学基金(7222076)
首都医科大学附属北京口腔医院青年科技创新人才培育计划(YSP202306)
出版年
2024
NETL
NSTL
万方数据