大泻脾汤通过靶向FOXK1-糖酵解轴逆转胃癌代谢重编程与诱导凋亡的研究OA
Mechanistic study of Daxiepi Decoction(大泻脾汤)in reversing metabolic reprogramming and inducing apoptosis in gastric cancer by targeting the FOXK1-glycolysis axis
目的 探讨大泻脾汤(DXP)通过调控叉头框转录因子K1(FOXK1)介导的糖酵解途径逆转胃癌细胞代谢重编程并诱导凋亡的作用机制.方法 构建FOXK1过表达的胃癌HGC-27细胞模型,采用含药血清干预,结合细胞毒性检测试剂盒(CCK-8)法、5-乙炔基-2'-脱氧尿嘧啶核苷(EdU)染色、免疫荧光、实时荧光定量聚合酶链反应(qPCR)及蛋白质印迹法(Western blot)等方法,分析DXP对己糖激酶2(hexokinase 2,HK2、丙酮酸激酶M2型(PKM2、乳酸脱氢酶A(LDHA)、葡萄糖代谢(葡萄糖含量、乳酸生成、三磷酸腺苷(ATP)水平)及B淋巴细胞瘤-2(Bcl-2/Bcl-2相关X蛋白(Bax)、半胱天冬酶-3(Caspase-3)的影响.结果 FOXK1过表达显著促进胃癌细胞增殖,上调GLUT1、HK2、PKM2、LDHA mRNA表达并抑制凋亡反应Bcl-2mRNA升高、Bax、Caspase-3 mRNA降低.30％-40％DXP含药血清72 h显著抑制FOXK1表达(P<0.01),葡萄糖含量升高、乳酸生成、ATP水平降低,同时Bcl-2降低、Bax、Caspase-3升高.联合实验表明,大泻脾汤能拮抗FOXK1过表达引发的代谢重编程与抗凋亡效应.结论 大泻脾汤通过靶向抑制FOXK1-糖酵解轴,逆转Warburg效应驱动的代谢-凋亡失衡,从而抑制胃癌细胞恶性增殖.该研究首次从分子层面揭示敦煌医学"体用并调"理论的科学内涵,为中药复方干预肿瘤代谢重编程提供了新策略.
Objective To investigate the mechanism by which Daxiepi Decoction(大泻脾汤,DXP)reverses metabolic reprogramming and induces apoptosis in gastric cancer cells through regulating the Forkhead box K1(FOXK1)-mediated glycolytic pathway.Methods An FOXK1-overexpressing gastric cancer HGC-27 cell model was established.Cells were treated with drug-containing serum.The effects of DXP were assessed using the CCK-8 assay,EdU staining,immunofluorescence(IF),qPCR,and Western blot(WB).Mea-surements included HK2,PKM2,LDHA,glucose metabolism parameters(glucose consumption,lactate production,adenosine triphos-phate/ATP levels),and apoptosis-related markers(Bcl-2,Bcl-2-associated X protein/Bax,and caspase-3).Results FOXK1 overex-pression promoted gastric cancer cell proliferation,up-regulated mRNA expression of GLUT1,HK2,PKM2,and LDHA,and sup-pressed apoptosis,indicated by increased Bcl-2 and decreased Bax and caspase-3 mRNA levels.Treatment with 30％-40％DXP-containing serum for 72 h significantly inhibited FOXK1 expression(P<0.01),increased glucose content,and decreased lactate pro-duction and ATP levels.Additionally,Bcl-2 expression was reduced,while Bax and caspase-3 were elevated.Combination experi-ments showed that DXP antagonized the metabolic reprogramming and anti-apoptotic effects induced by FOXK1 overexpression.Conclu-sion DXP may suppress malignant proliferation of gastric cancer cells by targeting the FOXK1-glycolysis axis and reversing the Warburg effect-driven metabolic-apoptotic imbalance.This study provides preliminary molecular evidence for the theory of"simultaneously regu-lating the structure and function"in Dunhuang medicine and suggests a potential new strategy for Chinese herbal medicine(CHM)com-pounds in targeting tumor metabolic reprogramming.
郭昊铭;李武龙;汪学鹏;卓淇泓;候晓琳;杨永琴;魏本君
甘肃中医药大学中医临床学院,甘肃 兰州 730000甘肃中医药大学中医临床学院,甘肃 兰州 730000甘肃中医药大学中医临床学院,甘肃 兰州 730000甘肃中医药大学中医临床学院,甘肃 兰州 730000甘肃中医药大学中医临床学院,甘肃 兰州 730000甘肃中医药大学中医临床学院,甘肃 兰州 730000甘肃中医药大学中医临床学院,甘肃 兰州 730000||甘肃省中医方药挖掘与创新转化重点实验室,甘肃 兰州 730000
医药卫生
大泻脾汤胃癌叉头框转录因子K1糖酵解细胞凋亡代谢重编程
Daxiepi Decoction(大泻脾汤)Gastric cancerFOXK1GlycolysisApoptosisMetabolic reprogramming
《时珍国医国药》 2026 (12)
2212-2220,9
国家自然科学基金(82260893)甘肃省自然科学基金资助项目(24JRRA1023)敦煌医学与转化教育部重点实验室开放基金(DHYX2023-03)
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