文献类型：期刊文献

中文题名：大泻脾汤调控FOXK1有氧糖酵解对胃癌荷瘤小鼠的影响

英文题名：Effects of Daxiepi Decoction(大泻脾汤)on gastric cancer-bearing mice via regulating aerobic glycolysis through FOXK1

作者：郭昊铭[1];候晓琳[1];汪学鹏[1];李武龙[1];卓淇泓[1];黄宇涵[1];杨永琴[1];魏本君[1,2]

第一作者：郭昊铭

机构：[1]甘肃中医药大学中医临床学院,甘肃兰州730000;[2]甘肃省中医方药挖掘与创新转化重点实验室,甘肃兰州730000

第一机构：甘肃中医药大学中医临床学院

年份：2026

卷号：37

期号：9

起止页码：1633

中文期刊名：时珍国医国药

外文期刊名：JOURNAL OF LI-SHIZHEN TRADITIONAL CHINESE MEDICINE

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金(82260893);甘肃省自然科学基金(24JRRA1023);敦煌医学与转化教育部重点实验室开放基金(DHYX2023-3)。

语种：中文

中文关键词：胃癌;大泻脾汤;有氧糖酵解;FOXK1

外文关键词：Gastric cancer;Daxiepi Decoction(大泻脾汤);aerobic glycolysis;FOXK1

摘要：目的探究大泻脾汤通过FOXK1调控有氧糖酵解对胃癌荷瘤小鼠的影响。方法建立荷瘤胃癌小鼠模型,将70只C57BL6小鼠,随机分为7组,每组10只,分别为正常组、模型组、大泻脾汤低剂量组(2.93g·kg^(-1)·d^(-1))、大泻脾汤中剂量组(5.85g·kg^(-1)·d^(-1))、大泻脾汤高剂量组(11.7g·kg^(-1)·d^(-1)),奥沙利铂组(10mg·kg^(-1))、2-DG组(1g·kg^(-1)·d^(-1))7个组;将通过蛋白免疫印迹法(Western blot)检测胃癌组织中叉头框K1(FOXK1)、己糖激酶2(HK2)、葡萄糖转运蛋白1(GLUT1)、丙酮酸激酶M2(PKM2)、乳酸脱氢酶A(LDHA)等糖酵解相关蛋白;免疫荧光法(IF)检测增殖细胞核抗原(Ki67)、葡萄糖转运蛋白1(GLUT1)蛋白含量;观察各组小鼠肿瘤质量;流式细胞分析技术检测肿瘤组织中肿瘤细胞的凋亡情况。电镜观察肿瘤细胞的微观结构。结果与空白组比较,模型组体质量降低(P<0.05);与模型组比较,各给药组组肿瘤生长明显抑制,体质量升高,瘤质量明显降低(P<0.05),各给药组凋亡率显著增加(P<0.05),各给药组肿瘤组织Western blot检测肿瘤组织中Foxk1、HK2、PKM2、LDHA等糖酵解蛋白以及Bcl-2凋亡相关蛋白表达水平明显降低(P<0.05);Bax、Caspase-3蛋白表达水平明显升高(P<0.05)。结论大泻脾汤可有效抑制肿瘤增长,增加肿瘤细胞凋亡比例,该作用可能是通过降低FOXK1蛋白水平,抑制有氧糖酵解反应,最终促进凋亡而实现。
Objective To investigate the effects of Daxiepi Decoction(大泻脾汤,DXPD)on gastric cancer-bearing mice via regulating FOXK1 and aerobic glycolysis.Methods A gastric cancer xenograft mouse model was established.Seventy C57BL/6 mice were randomly divided into seven groups(n=10 per group):normal control,model control,low/medium/high-dose DXPD(2.93 g·kg^(-1)·d^(-1),5.85 g·kg^(-1)·d^(-1),11.7 g·kg^(-1)·d^(-1)),oxaliplatin(10 mg·kg^(-1)),and 2-DG(1 g·kg^(-1)·d^(-1)).Protein expression of glycolysis-related markers including forkhead box K1(FOXK1),hexokinase 2(HK2),glucose transporter 1(GLUT1),pyruvate kinase M2(PKM2),and lactate dehydrogenase A(LDHA),as well as apoptosis-related proteins(Bcl-2,Bax,Caspase-3),was detected by Western blot(WB).Immunofluorescence(IF)was used to assess Ki67 and GLUT1 levels.Tumor mass was measured.Apoptosis rate was analyzed by flow cytometry(FCM).Ultrastructural changes in tumor cells were observed by electron microscopy.Results Compared with the normal group,the model group showed decreased body weight(P<0.05).Compared with the model group,all treatment groups exhibited significant inhibition of tumor growth,increased body weight,and reduced tumor mass(P<0.05).The apoptosis rate was significantly increased in all treatment groups(P<0.05).IF analysis showed decreased expression of Ki67 and GLUT1 in tumor tissues of the treatment groups.WB analysis showed that expression levels of FOXK1,HK2,PKM2,LDHA,and Bcl-2 were significantly decreased(P<0.05),while levels of Bax and Caspase-3 were increased(P<0.05).Conclusion DXPD can inhibit tumor growth and promote apoptosis in gastric cancer-bearing mice,which may be achieved by reducing FOXK1 protein levels,thereby inhibiting aerobic glycolysis.