文献类型：期刊文献

中文题名：康臻姬松茸提取物FA-2-b-β通过靶向HIF-1α调控的糖酵解而增敏肺癌化疗

英文题名：Kangzhen Agaricus blazei Murrill extract FA-2-b-βsensitizes lung can?cer chemotherapy by targeting HIF-1α-regulated glycolysis

作者：王彩霞[1];范俊顺[1];刘露[1];王倩凤[2];孙延庆[1,2]

第一作者：王彩霞

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃省人民医院,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2026

卷号：42

期号：5

起止页码：884

中文期刊名：中国病理生理杂志

外文期刊名：Chinese Journal of Pathophysiology

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(No.22JR11RA269);甘肃省自然科学基金专项优秀博士生项目(No.26JRRA764);甘肃中医药大学研究生“创新之星”项目(No.2026CXZX-907)。

语种：中文

中文关键词：康臻姬松茸;FA-2-b-β;肺癌;缺氧诱导因子1α;糖酵解

外文关键词：Kangzhen Agaricus blazei Murrill;FA-2-b-β;lung cancer;hypoxia-inducible factor-1α;glycolysis

摘要：目的:探讨康臻姬松茸提取物FA-2-b-β在体内外对肺癌的抑制作用,并重点阐明其是否通过靶向缺氧诱导因子1α(HIF-1α)/糖酵解轴与顺铂发挥协同增效及减毒作用。方法:采用肺癌细胞系及小鼠同种移植瘤模型,体内实验设立对照组、FA-2-b-β(50、100和200 mg/kg)单药组、顺铂单药组及联合用药组,体外实验设置不同浓度FA-2-b-β组。通过CCK8、集落形成、划痕愈合和Transwell侵袭实验检测细胞活力、集落形成、迁移和侵袭;通过Annexin V-FITC/PI双染法检测细胞凋亡;通过检测小鼠Lewis肺癌(LLC)细胞葡萄糖消耗、乳酸生成及细胞外酸化率评估糖代谢水平;采用RT-qPCR和Western blot检测HIF-1α信号通路及其下游关键糖酵解相关蛋白[葡萄糖转运蛋白1(GLUT1)、己糖激酶2(HK2)、丙酮酸激酶M2(PKM2)和乳酸脱氢酶A(LDHA)]的表达,并通过HIF-1α过表达实验进行机制验证。结果:体外实验表明,FA-2-b-β能以剂量依赖性方式显著抑制LLC细胞的活力、集落形成、迁移和侵袭,并诱导细胞凋亡。机制研究表明,FA-2-b-β可显著降低HIF-1α、GLUT1、HK2、PKM2和LDHA的mRNA和蛋白表达水平,减少葡萄糖消耗与乳酸生成,逆转肺癌细胞的有氧糖酵解(Warburg效应);HIF-1α的过表达可逆转FA-2-b-β对糖酵解的抑制作用。体内实验证实,与顺铂单药相比,FA-2-b-β与顺铂联合治疗能更显著地抑制移植瘤生长(P<0.01),并完全逆转由顺铂单药引起的小鼠体重下降等毒副作用,展现出显著的“减毒增效”协同效应。结论:康臻姬松茸提取物FA-2-b-β能够通过抑制HIF-1α/糖酵解信号轴,有效抑制肺癌细胞的增殖与侵袭,并与顺铂产生协同抗肿瘤效应,同时显著减轻顺铂的毒副作用。
AIM:This study aims to investigate the in vitro and in vivo inhibitory effects of Kangzhen Agaricus blazei Murrill extract FA-2-b-βon lung cancer,focusing on its potential synergistic antitumor and detoxification effects with cisplatin via the hypoxia-inducible factor-1α(HIF-1α)/glycolysis axis.METHODS:Lung carcinoma cell lines and a mouse xenograft tumor model were used.Experimental groups included control,FA-2-b-βmonotherapy(50,100 and 200 mg/kg),cisplatin monotherapy,and combination therapy groups.Cell viability,colony formation,migration and invasion were assessed using CCK8,colony formation,wound-healing and Transwell invasion assays,respectively.Apoptosis was detected by Annexin V-FITC/PI staining.Glycolytic metabolism was evaluated by measuring glucose consumption,lactate production and extracellular acidification rate.The expression levels of HIF-1αand glycolytic enzymes[glucose transporter 1(GLUT1),hexokinase 2(HK2),pyruvate kinase M2(PKM2)and lactate dehydrogenase A(LDHA)]were analyzed using RT-qPCR and Western blot.Mechanistic validation was performed using HIF-1αoverexpression experiments.RESULTS:In vitro,FA-2-b-βsignificantly inhibited Lewis lung carcinoma(LLC)cell viability,colony formation,migration and invasion in a dose-dependent manner and induced apoptosis.Mechanistic studies revealed that FA-2-b-βsignificantly down-regulated the mRNA and protein expression levels of HIF-1α,GLUT1,HK2,PKM2 and LDHA,reduced glucose consumption and lactate production,thereby reversing the Warburg effect.Overexpression of HIF-1αrescues the inhibitory effect of FA-2-b-βon glycolysis.In vivo experiments confirmed that combined FA-2-b-βand cisplatin inhibited xenograft tumor growth more significantly than cisplatin monotherapy(P<0.01)and completely reversed cisplatininduced side effects,such as body weight loss,demonstrating a notable"synergistic efficacy enhancement and toxicity reduction"effect.CONCLUSION:These findings indicate that the Agaricus blazei Murrill extract FA-2-b-βsuppresses the proliferation and invasion of LLC by inhibiting the HIF-1α/glycolysis signaling axis.Moreover,FA-2-b-βdemonstrates a synergistic antitumor effect with cisplatin and effectively mitigates its associated toxicities,highlighting its potential as a promising adjunctive agent in treatment of lung cancer.