中药活性成分抑制抗凋亡蛋白抗肿瘤研究进展

Research progress in inhibiting anti-apoptotic proteins of active components of traditional Chinese medicine for anti-tumor

肿瘤的发生是细胞增殖和凋亡失衡的结果。肿瘤抗凋亡的重要调节机制之一是肿瘤细胞通过表达抗凋亡蛋白从而对凋亡产生耐受,近年来以抗凋亡蛋白为靶点的肿瘤治疗研究在临床抗癌药物研发中备受关注。目前已发现的具有抗凋亡作用的蛋白主要有参与内源凋亡途径的B淋巴细胞瘤-2基因(Bcl-2)、细胞凋亡抑制蛋白(IAPs)家族以及参与外源凋亡途径的细胞型Fas相关死亡域蛋白样白介素-1转换酶抑制蛋白(c-FLIP)。寻找高效低毒的抗肿瘤药物一直是肿瘤治疗的研究热点,其中抑制抗凋亡蛋白的中药天然活性成分逐渐成为现代抗肿瘤药物开发的新趋势。文章主要对抑制抗凋亡蛋白的中药及天然药物活性成分从化学成分及作用机制的角度进行总结及综述,为抗肿瘤中药的新药发现和机制研究提供参考及理论依据。

Tumorigenesis is the result of imbalance between cell proliferation and apoptosis. One of the important mechanisms of antiapoptosis in tumor tissue is that tumor cells become resistant to apoptosis by expressing anti-apoptotic proteins. In recent years,the cancer therapy targeting the anti-apoptotic protein has attracted much attention in clinic research. The main anti-apoptotic proteins are Bcell lymphoma-2 (Bcl-2) involved in endogenous apoptosis pathway,apoptosis inhibitor proteins (IAPs) and cellular FADD-like IL-1β converting enzyme-inhibitory protein (c-FLIP) which is involved in exogenous apoptosis pathway. The exploration of anti-tumor drugs with high efficiency and low toxicity has always been a research hotspot in tumor therapy. The natural active components of traditional Chinese medicine (TCM),which inhibit anti-apoptotic proteins,have become a new trend of modern anti-tumor drugs. Herein,to provide references and theoretical basis for the discovery and clarify the mechanism of novel anti-tumor drugs from TCM,we reviewed and summarized the chemical composition and molecular mechanisms of the active components from TCM and natural products that inhibit anti-apoptotic proteins.