二氢丹参酮I通过靶向核FBXW11/LTN1/PKM2轴抑制糖酵解和胃癌生长
Dihydrotanshinone I suppresses glycolysis and gastric cancer growth by targeting the nuclear FBXW11/LTN1/PKM2 axis.
摘要(中文译文)
胃癌（GC）是全球重大健康问题，尤其在亚洲地区。二氢丹参酮I（DHT）是一种从丹参中分离得到的天然来源且可商业获得的化合物，通过调节肿瘤代谢表现出潜在的抗胃癌活性。本研究旨在探讨DHT的抗胃癌作用，并阐明DHT调控糖酵解的分子机制。研究采用整合分子谱分析、功能实验和临床样本分析来评估DHT在胃癌中的药理作用及机制。通过RNA测序、染色质免疫沉淀测序和免疫沉淀-质谱联用技术鉴定了DHT调控的药理靶点和信号通路。利用体外实验和体内模型进行功能验证。分析临床胃癌标本中靶基因表达、临床病理特征与患者预后之间的关联。DHT在低浓度下选择性抑制胃癌细胞增殖，而对正常胃上皮细胞无明显影响。核内FBXW11被鉴定为直接靶点，且在胃癌组织中表达上调。这种上调与晚期TNM分期和不良预后相关。抑制核内FBXW11表达可降低糖酵解、侵袭和增殖能力。机制上，DHT促进LTN1介导的PKM2泛素-蛋白酶体降解，从而抑制糖酵解。二氢丹参酮I通过FBXW11/LTN1/PKM2轴抑制胃癌进展，凸显其作为一种低毒性、具有转化意义且靶向代谢的植物化学物的潜力。与先前报道的DHT涉及氧化应激、DNA损伤或免疫调节的机制不同，本研究揭示了胃癌中一个此前未被认识的核内泛素化介导的代谢调控轴。
Abstract
Gastric cancer (GC) is a major global health problem, particularly in Asia. Dihydrotanshinone I (DHT), a naturally derived and commercially available compound isolated from Salvia miltiorrhiza, exhibits potential anti-GC activity through the modulation of cancer metabolism. This study aimed to investigate the anti-GC effects of DHT and elucidate the molecular mechanisms through which DHT regulates glycolysis. Integrated molecular profiling, functional experiments, and clinical sample analyses were employed to evaluate the pharmacological effects and mechanism of DHT in gastric cancer. The pharmacological targets and signaling pathways regulated by DHT were identified using RNA sequencing, chromatin immunoprecipitation sequencing, and immunoprecipitation-mass spectrometry. Functional validation was performed using in vitro assays and in vivo models. Clinical GC specimens were analyzed for associations between target gene expression, clinicopathological features, and patient prognosis. DHT selectively inhibited GC cell proliferation at low concentrations while sparing normal gastric epithelial cells. Nuclear FBXW11 was identified as a direct target and was upregulated in GC tissues. This upregulation was correlated with advanced TNM stage and poor prognosis. The suppression of nuclear FBXW11 expression reduced glycolysis, invasion, and proliferation. Mechanistically, DHT promoted the LTN1-mediated ubiquitin-proteasome degradation of PKM2, thus suppressing glycolysis. Dihydrotanshinone I suppresses GC progression via the FBXW11/LTN1/PKM2 axis, highlighting its potential as a metabolism-targeting phytochemical with low toxicity and translational relevance. Unlike previously reported DHT mechanisms involving oxidative stress, DNA damage, or immune modulation, our findings reveal a previously unrecognized nuclear ubiquitination-mediated metabolic regulatory axis in gastric cancer.
如何引用
AMA
Yunmeng Nie, Xing Bai, Mingsi Zhang, Xiaojuan Liu, Tao Jiang, Guangji Zhang. Dihydrotanshinone I suppresses glycolysis and gastric cancer growth by targeting the nuclear FBXW11/LTN1/PKM2 axis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158254.
APA
Yunmeng Nie, Xing Bai, Mingsi Zhang, Xiaojuan Liu, Tao Jiang, Guangji Zhang (2026). Dihydrotanshinone I suppresses glycolysis and gastric cancer growth by targeting the nuclear FBXW11/LTN1/PKM2 axis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158254
GB/T 7714
Yunmeng Nie, Xing Bai, Mingsi Zhang, Xiaojuan Liu, Tao Jiang, Guangji Zhang. Dihydrotanshinone I suppresses glycolysis and gastric cancer growth by targeting the nuclear FBXW11/LTN1/PKM2 axis.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158254.
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