沙蟾毒精抗癌活性及相关机制的研究进展

Research progress in the anti-cancer activity and related mechanisms of arenobufagin

蟾酥是一种具活性的蟾蜍提取物,其炮制方法是将中华大蟾蜍皮肤腺和耳后腺分泌的毒液进行酒制或高温干燥而得。作为一种在中国被用来治疗疾病已有上千年历史的天然产物,蟾酥具有强心、镇痛、抗心肌缺血、抗内毒素休克、抗癌等多种药理作用。沙蟾毒精(arenobufagin,ARE)是蟾酥的主要化学成分之一,其抗癌机制也在近十年来被越来越多地阐明。ARE可通过多种途径发挥抗癌作用,如诱导癌细胞凋亡和/或自噬、坏死、细胞周期阻滞,抑制癌细胞迁移和侵袭,抑制血管生成等。目前有关ARE的研究主要关注在其癌细胞选择性毒性和抗癌分子机制方面,多为细胞和动物水平。受限于ARE毒副作用较大、靶点不明确和药代动力特性不清楚等,ARE尚未进入西医临床应用阶段。该文梳理了ARE的抗癌活性、抗癌分子机制以及与其他抗癌药物联合使用的相关研究成果,以期为完善ARE的抗癌机制研究提供新的方向。

Toad venom is an active extract of toad,which is processed by distilling or drying at high temperature the venom secreted from the skin glands and ear-side glands of Toad Chinensis.As a natural product that has been used to treat diseases in China for thousands of years,toad venom has many pharmacological effects such as heart strengthening,analgesia,anti-myocardial ischemia,anti-endotoxin shock,and anti-cancer.Arenobufagin(ARE)is one of the main chemical components of toad venom,and its anti-cancer mechanism has been increasingly clarified in the past decade.ARE can play an anti-cancer role through a variety of ways,such as inducing apoptosis and/or autophagy of cancer cells,necrosis,and cell cycle arrest,inhibiting cancer cell migration and invasion,and inhibiting angiogenesis.The current research on ARE mainly focuses on the selective toxicity of cancer cells and the molecular mechanism of anti-cancer,mostly at the cellular and animal levels.Due to the large toxic and side effects of ARE,unclear targets and unclear pharmacokinetic characteristics,ARE has not yet entered the clinical application in Western medicine.This article summarizes relevant research results on the anti-cancer activity and molecular mechanism of ARE,and its combination with other anti-cancer drugs in order to provide a new direction for improving the anti-cancer mechanism of ARE.