4'‑羟基查耳酮抑制胃癌细胞活力及c‑Myc介导的葡萄糖摄取和糖酵解作用OA
4'‑Hydroxychalcone suppresses gastric cancer cell viability and c‑Myc mediated glucose uptake and glycolysis
目的 探究4'-羟基查耳酮(4-HC)对胃癌细胞增殖、凋亡、能量代谢的影响及其可能存在的分子机制.方法 采用细胞计数试剂盒(CCK-8)法检测细胞活力;使用膜联蛋白V/碘化丙啶(Annexin V/PI)凋亡试剂盒检测胃癌细胞的凋亡率;使用葡萄糖摄取荧光探针(2-NBDG)检测人胃癌HGC-27细胞的葡萄糖摄取水平;不同浓度4‐HC处理、过表达细胞髓细胞瘤病原癌基因(c⁃Myc)联合4‐HC处理或沉默c⁃Myc(siRNA c-Myc)联合4‐HC处理后,采用Western blot法检测细胞增殖、凋亡、葡萄糖摄取及能量代谢相关蛋白的表达.结果 4-HC可显著抑制3种胃癌细胞的活力.12.5、25、50 μmol/L 4-HC干预后,HGC-27细胞凋亡率分别为14.24%、51.82%和80.95%.4-HC(9、15、18 h)可显著降低HGC-27细胞葡萄糖摄取能力.4-HC(25、50 μmol/L)能显著抑制HGC-27细胞的增殖、葡萄糖摄取及能量代谢相关蛋白的表达,同时上调凋亡相关蛋白的表达.c-Myc过表达能够拮抗4-HC对胃癌细胞活力的抑制作用及其对胃癌细胞增殖、凋亡以及葡萄糖摄取、能量代谢相关蛋白表达的调控作用.siRNA c-Myc则进一步促进4-HC的细胞活力抑制作用及其对葡萄糖摄取和能量代谢相关蛋白表达的抑制作用.哺乳动物雷帕霉素靶蛋白(mTOR)激动剂(MHY1485)能拮抗4-HC对HGC-27细胞活力的抑制作用.结论 4-HC可显著抑制胃癌细胞活力和细胞增殖,并促进细胞凋亡,其作用机制与其抑制mTOR/c-Myc轴介导的胃癌细胞葡萄糖摄取和糖酵解有关.
Objective To investigate the effect of 4'‐hydroxychalcone(4-HC)on the proliferation,apoptosis and energy metabolism of gastric cancer cells and its possible molecular mechanisms.Methods Cell Counting Kit‐8(CCK‐8)was used to monitor cell viability;Annexin V/Propidium Iodide(PI)apoptosis kit was used to assess the apoptosis rate of gastic cancer cells,and glucose uptake fluorescent probe(2-NBDG)was used to evaluate glucose uptake in HGC-27 cells.Western blot was used to detect the expression of proteins involved in proliferation,apoptosis,glucose uptake,and energy metabolism,after treatments with various concentrations of 4‐HC,cellular-myelocytomatosis viral oncogene(c⁃Myc)overexpression combined with 4‐HC treatment,or silencing of c⁃Myc(siRNA c‐Myc)combined with 4‐HC treatment.Results 4-HC significantly inhibited the viability of kinds of gastric cancer cells.After treatment of 4-HC at concentrations of 12.5,25 and 50 μmol/L,the apoptosis rates of HGC-27 cells were 14.24%,51.82%,and 80.95%,respectively.Moreover,4-HC(9,15,18 h)could significantly decrease the glucose uptake in HGC-27 cells.4-HC(25,50 μmol/L)could significantly suppress the proliferation,glucose uptake and the expression of energy metabolism-related proteins in HGC-27 cells,while it could also up‐regulate the expression of apoptosis-related proteins.Additionally,c-Myc overexpression could counteract the inhibitory effect of 4-HC on the cell viability of gastric cancer cells,as well as its regulatory effects on the proliferation,apoptosis and the expression of glucose uptake and energy metabolism-related proteins of HGC-27 cells.siRNA c-Myc further enhanced the inhibitory effect of 4-HC on cell viability,as well as its suppressive effect on the protein expression of glucose uptake and energy metabolism-related proteins of HGC-27 cells.mTOR agonist(MHY1485)can reverse the 4-HC-induced reduction in cell viability of HGC-27 cells.Conclusions 4-HC significantly inhibits the gastric cancer cell viability and cell proliferation,and promotes apoptosis.Its mechanism is associated with the suppression of the mTOR/c‐Myc axis-mediated glucose uptake and glycolysis.
刘娇安;李昱彤;张玉杰;费晓燕;吴辉;黄菲;吴晓俊;张德高;石海莲
上海市复方中药重点实验室,教育部中药标准化重点实验室,国家中医药管理局中药新资源与品质评价重点研究室,上海中药标准化研究中心,上海中医药大学中药研究所(上海 201203)上海市复方中药重点实验室,教育部中药标准化重点实验室,国家中医药管理局中药新资源与品质评价重点研究室,上海中药标准化研究中心,上海中医药大学中药研究所(上海 201203)上海市复方中药重点实验室,教育部中药标准化重点实验室,国家中医药管理局中药新资源与品质评价重点研究室,上海中药标准化研究中心,上海中医药大学中药研究所(上海 201203)上海中医药大学附属龙华医院脾胃病一科(上海 200032)上海市复方中药重点实验室,教育部中药标准化重点实验室,国家中医药管理局中药新资源与品质评价重点研究室,上海中药标准化研究中心,上海中医药大学中药研究所(上海 201203)上海市复方中药重点实验室,教育部中药标准化重点实验室,国家中医药管理局中药新资源与品质评价重点研究室,上海中药标准化研究中心,上海中医药大学中药研究所(上海 201203)上海市复方中药重点实验室,教育部中药标准化重点实验室,国家中医药管理局中药新资源与品质评价重点研究室,上海中药标准化研究中心,上海中医药大学中药研究所(上海 201203)上海健康医学院附属崇明医院药剂科/科研科(上海 202150)上海市复方中药重点实验室,教育部中药标准化重点实验室,国家中医药管理局中药新资源与品质评价重点研究室,上海中药标准化研究中心,上海中医药大学中药研究所(上海 201203)
胃癌4'-羟基查耳酮甘草肿瘤能量代谢凋亡增殖
gastric cancer4'-hydroxychalconeGlycyrrhizae Radix et Rhizomatumorenergy metabolismapoptosisproliferation
《上海中医药杂志》 2026 (10)
68-79,12
国家自然科学基金项目(82474132)上海市自然科学基金项目(23ZR1463100)上海市复方中药重点实验室开放课题项目(21DZ2270500)
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