蟾酥中蟾蜍二烯内酯类化学成分抗肿瘤分子机制研究进展OA
Research progress in antitumor molecular mechanisms of bufadienolides in Bufonis Venenum
蟾酥为蟾蜍科动物耳后腺及皮肤腺的干燥分泌物,其抗肿瘤活性主要源于蟾蜍二烯内酯类成分.该文系统综述了近五年来蟾蜍二烯内酯类成分(包括华蟾酥毒基、蟾毒灵、脂蟾毒配基、蟾毒它灵、沙蟾毒精、日蟾毒它灵及华蟾毒它灵)在恶性肿瘤治疗中的分子机制研究进展.现有研究表明,该类成分通过多靶点、多通路调控发挥广谱抗肿瘤效应:在抑制肿瘤细胞增殖方面,主要调控丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/AKT)及信号转导及转录激活因子 3(STAT3)等信号通路;在诱导细胞死亡方面,可通过线粒体途径凋亡、铁死亡及自噬等多种方式清除肿瘤细胞;在抑制侵袭转移方面,可调控上皮-间充质转化(EMT)、基质金属蛋白酶(MMP)表达及肿瘤微环境中巨噬细胞极化;此外,该类成分还可抑制肿瘤血管生成、增强化疗药物敏感性、激活抗肿瘤免疫应答及调控表观遗传修饰.联合用药研究表明,蟾蜍二烯内酯类成分与临床化疗药物联用可产生协同增效作用,含该类成分的中药制剂亦展现出多靶点调控的抗肿瘤特性.该文系统梳理蟾蜍二烯内酯类成分的抗肿瘤分子机制,旨在为其深入研究和临床转化提供理论依据.
Bufonis Venenum,the dried secretory product from the postauricular and cutaneous glands of Bufonidae,exerts antitumor activity primarily through bufadienolides.This review systematically summarizes the molecular mechanisms of key bufadienolides,including cinobufagin,bufalin,resibufogenin,bufotalin,arenobufagin,gamabufotalin,and cinobufotalin,in the treatment of malignant tumors over the past five years.Current evidence demonstrates that these compounds exert broad-spectrum antitumor effects through multi-target and multi-pathway modulation.In inhibiting tumor cell proliferation,these compounds primarily regulate signaling pathways such as mitogen-activated protein kinase(MAPK),phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT),and signal transducer and activator of transcription 3(STAT3).In inducing cell death,they eliminate malignant cells through multiple modalities including mitochondrion-mediated apoptosis,ferroptosis,and autophagy.In suppressing invasion and metastasis,they modulate epithelial-mesenchymal transition(EMT),matrix metalloproteinase(MMP)expression,and macrophage polarization within the tumor microenvironment.Furthermore,these compounds inhibit angiogenesis,enhance chemosensitivity,activate antitumor immune responses,and regulate epigenetic modifications.Combination therapy studies reveal that bufadienolides exhibit synergistic efficacy when being combined with clinical chemotherapeutic agents,and TCM preparations containing these compounds demonstrate antitumor properties through multi-target regulation.This review elucidates the antitumor molecular mechanisms of bufadienolides,aiming to provide a theoretical basis for further mechanism investigation and clinical translation.
王宁宁;岳元雷;刘名玉
山东中医药大学 中医药创新研究院,山东 济南 250355山东第一医科大学附属颈肩腰腿痛医院 康复医学科,山东 济南 250000山东中医药大学 中医药创新研究院,山东 济南 250355
蟾酥蟾蜍二烯内酯类抗肿瘤增殖凋亡侵袭与转移自噬血管生成
Bufonis Venenumbufadienolidesantitumorproliferation and apoptosisinvasion and metastasisautophagyangiogenesis
《中国中药杂志》 2026 (11)
3128-3142,15
山东省自然科学基金项目(ZR2022QH159)山东省博士后创新计划项目(SDCX-ZG-202203068)
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