双氢青蒿素抗肿瘤分子生物学机制研究进展  

Progress on anti-tumor molecular mechanisms of dihydroartemisinin

作　　者：曹鹏[1] 冷东瑾 李滢[1] 张紫薇[1] 刘磊[1] 李晓岩[1] 

机构地区：[1]东北林业大学生命科学学院

出　　处：《浙江大学学报（医学版）》2016年第5期501-507,共7页Journal of Zhejiang University(Medical Sciences)

基　　金：中央高校基本科研业务费专项资金(2572014CA23);中国博士后科学基金(2013M541328);东北林业大学大学生创新创业训练计划(201510225150)

摘　　要：青蒿素作为抗疟特效药在临床应用中存在水溶性小、口服效果差等缺点，因此研究人员开发了保留其母核的多种衍生物。其中双氢青蒿素（DHA）的抗疟活性更强，且具有在体内代谢速度快、水溶性好等优点，同时DHA对肿瘤细胞也有良好的抑制效果，且其分子生物学作用机制与自身结构中的过氧桥密切相关。由于肿瘤细胞比正常细胞需要摄取更多的铁离子，因此肿瘤细胞膜上存在大量的转铁蛋白受体。DHA能在亚铁离子的存在下使过氧桥发生断裂，产生自由基从而对肿瘤细胞发挥杀伤作用，并能使转铁蛋白受体发生内吞，阻止肿瘤细胞从外界摄入必需的铁离子。本文主要从DHA加速细胞氧化损伤、诱导肿瘤细胞凋亡、抑制肿瘤细胞生长增殖和侵袭转移以及逆转肿瘤细胞多药耐药等方面对其抗肿瘤的分子生物学机制进行综述。Artemisinin is an anti-malarial drug with poor water solubility and oral absorption; so a variety of derivatives based on the parent nucleus have been developed. Compared with artemisinin, dihydroartemisinin （DHA） has a stronger antimalaria activity, and has the advantages of high metabolic rate and better water solubility. Recent studies have discovered that DHA has a good inhibitory effect on tumor cells, which is closely related to the peroxide bridge in its molecular structure.Since tumor cells need more Fe3＋ than normal ceils, there are a large number of transferrin receptors on the tumor cell membrane. DHA can break the peroxide bridge in the presence of Fe2＋ , and the free radicals generated can play its lethal effect on tumor ceils. In addition, DHA can promote endocytosis of transferrin receptor, and thus prevent cancer cells from taking Fe3＋ from microenvironment. This article reviews the anti-tumor molecular mechanism of DHA, including accelerating oxidative damage inducing apoptosis, inhibiting the growth, proliferation and invasion of tumor ceils, reversing tumor muhidrug resistance.

关 键 词：青蒿素/类似物和衍生物 青蒿素/药理学 抗肿瘤药(中药)/治疗应 用 细胞凋亡/药物作用 细胞增殖/药物作用 肿瘤侵润 肿瘤转移 综述 

分 类 号：R285[医药卫生—中药学]