文献类型：期刊文献

中文题名：甘草次酸衍生物的合成及其抗肝癌活性

英文题名：Research on the anti-hepatocellular carcinoma activityand mechanisms of glycyrrhetinic acid derivatives

作者：崔旭鑫[1,2];崔文平[1,2];毕艳兴[1,2];成帆[1,2];李育宁[1,2];张宝来[3];赵全义[4];杨孝来[2,5]

第一作者：崔旭鑫

机构：[1]甘肃中医药大学药学院,甘肃兰州730000;[2]甘肃省人民医院药剂科,甘肃兰州730000;[3]兰州大学基础医学院,甘肃兰州730000;[4]兰州大学药学院,甘肃兰州730020;[5]甘肃省人民医院研究型病房,甘肃兰州730000

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

年份：2025

卷号：41

期号：11

起止页码：2150

中文期刊名：中国药理学通报

外文期刊名：Chinese Pharmacological Bulletin

收录：;北大核心:【北大核心2023】；

基金：甘肃省自然科学基金资助项目(No22JR5RA507)。

语种：中文

中文关键词：甘草次酸;合成;衍生物;抗肿瘤活性;肝癌;细胞凋亡

外文关键词：glycyrrhetinic acid;synthesis;derivatives;antitumor activity;hepatocellular carcinoma;cell apoptosis

摘要：目的 以甘草次酸为母核,设计合成一系列衍生物,并对其进行抗肿瘤活性筛选,对活性最优化合物进行体内外抗肿瘤作用及机制研究。方法MTT法筛选出抗肿瘤活性最优的化合物;MTT法、划痕实验、平板克隆实验和Transwell迁移实验检测化合物对肿瘤细胞活性和迁移能力的影响;流式细胞术检测化合物对肿瘤细胞周期和凋亡的影响;蛋白印迹实验检测对促凋亡蛋白Bax、caspase-3、cleaved caspase-3的影响;建立小鼠肝癌腹水瘤模型,检测化合物体内的抗肿瘤作用。结果 筛选出化合物C22对肝癌细胞的抑制作用最为明显;C22以时间-浓度依赖性抑制肝癌细胞的活性和迁移;化合物C22能上调肝癌细胞中促凋亡蛋白Bax、caspase-3、cleaved caspase-3的表达,诱导细胞凋亡并阻滞细胞周期于G_(0)/G_(1)、S期;化合物C22能明显抑制小鼠肝癌腹水瘤的生长,延长生存期。结论 甘草次酸衍生物C22能够明显抑制肝癌细胞的活性和迁移能力,阻滞细胞周期,诱导细胞凋亡,并且能抑制肝癌腹水的生成,延长生存期。
Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the compound with the most potent antitumor activity.MTT assay,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and migration.Flow cytometry was employed to assess the impact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was established to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepatocellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upregulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular carcinoma cells,induced apoptosis,and arrested the cell cycle in the G_(0)/G_(1) and S phases.C22 significantly reduced the growth of mouse hepatocellular carcinoma ascites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.