西南民族药用植物野坝子抗胃癌的作用机制  

Anti-gastric cancer mechanism of Southwest ethnomedicinal plant Elsholtzia rugulosa Hemsl.

作　　者：于琼 宋雅雅 危志强 余卫星 贺婉娜 刘立亚[3,4] 龙春林[1,3,4,5] YU Qiong;SONG Yaya;WEI Zhiqiang;YU Weixing;HE Wanna;LIU Liya;LONG Chunlin(Key Laboratory of Ethnomedicine of Ministry of Education,Minzu University of China,Beijing 100081,China;College of Pharmacy,Minzu University of China,Beijing 100081,China;Key Laboratory of Ecology and Environment in Minority Areas,National Ethnic Affairs Commission,Minzu University of China,Beijing 100081,China;College of Life and Environmental Sciences,Minzu University of China,Beijing 100081,China;Institute of National Security Studies,Minzu University of China,Beijing 100081,China)

机构地区：[1]中央民族大学民族医药教育部重点实验室,北京100081 [2]中央民族大学药学院,北京100081 [3]中央民族大学民族地区生态环境国家民委重点实验室,北京100081 [4]中央民族大学生命与环境科学学院,北京100081 [5]中央民族大学国家安全研究院,北京100081

出　　处：《中华中医药杂志》2024年第7期3696-3704,共9页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.32370407,No.31870316);国家自然科学基金国际(地区)合作项目(No.31761143001);民族医药教育部重点实验室开放项目(No.KLEM-ZZ202303);民族地区生态环境国家民委重点实验室(中央民族大学)自主课题(No.KLEEMA202202);云南省项目(No.202305AF150121,No.GBP-2022-01)。

摘　　要：目的:基于网络药理学和分子对接技术,探讨野坝子治疗胃癌的有效成分、作用靶点以及作用机制,并通过体外细胞实验进行验证。方法:采用超高效液相色谱-串联质谱(UPLC-MS/MS)技术对野坝子水提物进行化学成分分析与鉴定,基于这些成分运用网络药理学工具筛选野坝子治疗胃癌的有效成分与作用靶点,构建“活性成分-靶点”网络,预测相关信号通路;体外细胞实验检测野坝子对胃癌MGC-803细胞增殖、迁移、侵袭和凋亡的影响,并利用Western Blot法检测相关蛋白表达水平变化。结果:网络药理学分析显示,野坝子可通过咖啡酸苯乙酯、高车前素等关键成分作用PI3K-Akt通路等途径上的核心靶点发挥抗胃癌作用。细胞实验结果显示,与对照组比较,0.01、0.05、0.10 mg/mL野坝子水提物显著抑制了MGC-803胃癌细胞的增殖活性,并能有效诱导细胞凋亡。此外,0.01、0.025、0.05 mg/mL野坝子水提物还能显著抑制MGC-803细胞的迁移与侵袭。Western Blot结果显示,与对照组比较,经0.05、0.10 mg/mL野坝子水提物处理后的细胞,其p-Akt、Bcl-2、MMP-2及MMP-9蛋白表达水平呈现下调趋势,促凋亡蛋白Bax表达显著增加(P<0.05)。结论:野坝子可通过多成分、多靶点调控PI3K-Akt通路等途径实现杀伤胃癌细胞的作用。Objective:To investigate the active ingredients,targets and mechanisms of action of Elsholizia rugulosa Hemsl.against gastric cancer based on network pharmacology and molecular docking techniques,and to further validate them through in vitro cellular assays.Methods:The aqueous extracts of Elsholtzia rugulosa Hemsl.were analyzed and identified by UPLC-MS/MS.The active ingredients and targets of Elsholtzia rugulosa Hemsl.for the treatment of gastric cancer were screened based on these ingredients using network pharmacology tools to construct an'active ingredient-target'network and to predict the relevant signaling pathways.In vitro cellular assays were performed to detect the Elsholtzia rugulosa Hemsl.on the proliferation,migration,invasion and apoptosis of gastric cancer MGC-803 cells,and the changes in protein expression by Western Blot.Results:The network pharmacological analysis showed that Elsholtzia rugulosa Hemsl.could play a role in killing gastric cancer cells by acting on the core targets of the PI3K-Akt pathway and other pathways through key components such as caffeic acid phenethyl ester and gossypol,and so on.The results of the cell experiment demonstrated that,compared with the control group,the water extract of Elsholtzia rugulosa Hemsl.exhibited significant inhibitory effects on the proliferation activity of MGC-803 gastric cancer cells and effectively induced cellular apoptosis within a concentration range of 0.01,0.05,0.10 mg/mL.Furthermore,at concentrations of 0.01,0.025,0.05 mg/mL,the water extract of Elsholtzia rugulosa Hemsl.significantly suppressed both migration and invasion abilities of MGC-803 cells.Western Blot analysis revealed a downward trend in the expression levels of p-Akt,Bcl-2,MMP-2,and MMP-9 proteins in cells treated by of Elsholtzia rugulosa Hemsl.,there was a notable increase in proapoptotic protein Bax expression compared with the control group(P<0.05).Conclusion:Elsholtzia rugulosa Hemsl.can achieve anti-gastric cancer pharmacological effects through multi-component,multi-tar

关 键 词：野坝子 胃癌 网络药理学 细胞凋亡 细胞迁移 细胞侵袭 机制 成分 靶点 

分 类 号：R285[医药卫生—中药学]