解放军医学院学报2025，Vol.46Issue(7)：653-660,679,9.DOI:10.12435/j.issn.2095-5227.25040401
氨基酸代谢抑制剂V9302对胃癌恶性进展及糖酵解效应的影响与机制研究
Effect of amino acid metabolism inhibitor V9302 on malignant progression and glycolytic reprogramming of gastric cancer and its mechanisms
摘要
Abstract
Background Gastric cancer(GC)is one of the most lethal malignancies worldwide,with significant therapeutic challenges.V9302,an inhibitor targeting the alanine-serine-cysteine transporter 2(ASCT2),has been shown to suppress tumor growth and metabolism in various cancers;however,its functional roles and mechanisms in GC remain poorly understood.Objective To investigate the effects of V9302 on malignant behaviors and glycolytic regulation in GC cells.Methods ASCT2-high-expressing GC cell lines(AGS and MGC-803)were screened by Western blot(WB).The expression of key glycolytic enzymes,including hexokinase 2(HK2),phosphoglycerate mutase 1(PGAM1),and enolase 1(ENO1),was analyzed.Cell proliferation and migration were evaluated using CCK-8,colony formation,scratch wound healing,and Transwell assays.Proteomic profiling and bioinformatic analysis were performed to identify differentially expressed proteins in V9302-treated cells.Glycolytic activity was assessed by measuring glucose uptake,ATP production,pyruvate levels,and lactate secretion.A subcutaneous xenograft model in nude mice was established to evaluate the antitumor effects of V9302 in vivo.Results AGS and MGC-803 cells exhibited high ASCT2 expression.V9302 significantly inhibited GC cell proliferation(P<0.01)and migration(P<0.01).Proteomic analysis revealed that V9302 modulated glycolytic regulatory pathways in AGS cells.V9302 enhanced glycolytic flux,as evidenced by increased ATP production(P<0.05),pyruvate accumulation(P<0.01),glucose uptake(P<0.05),and lactate secretion(P<0.01),without altering the activity of key glycolytic enzymes.In vivo,V9302 suppressed tumor growth(P<0.05),reduced Ki-67(P<0.01)and PCNA(P<0.001)expression,and promoted apoptosis(TUNEL,P<0.001).Conclusion V9302 inhibits proliferation,migration,and induces apoptosis in GC cells both in vitro and in vivo.Mechanistically,V9302 enhances glycolytic activity by targeting metabolic regulatory networks,independent of canonical enzyme-driven pathways.These findings provide a theoretical basis for combining V9302 with glycolysis inhibitors to overcome metabolic adaptation in GC therapy.关键词
胃癌/肿瘤代谢/V9302/糖酵解/谷氨酰胺Key words
gastric cancer/tumor metabolism/V9302/glycolysis/glutamine分类
医药卫生引用本文复制引用
杜家俊,赵瑞阳,徐其轩,袁震,卫勃..氨基酸代谢抑制剂V9302对胃癌恶性进展及糖酵解效应的影响与机制研究[J].解放军医学院学报,2025,46(7):653-660,679,9.基金项目
国家自然科学基金面上项目(8227111040) （8227111040）
