雷公藤甲素逆转肿瘤耐药机制研究进展
The cancer cell resistance to current anticancer therapeutics as well as their causing side effects are still obstacles to successful cancer therapy.Hence,development of new anticancer agents or therapeutics are of vital significance, especially rational combination therapies containing low-cost natural products with multiple targets, which has attracted great interests. Triptolide, the main biocomponent of Tripterygium wilfordii Hook F, is restricted in clinical applications mainly due to its severe systemic toxicities, though it has shown strong antitumor activities in preclinical studies. Mounting evidences suggest that using triptolide at low doses as an adjuvant therapeutic agent circumvents resistance to current anticancer therapies, enhances the anticancer effectiveness, and relieves toxicities of both triptolide and anticancer therapies. The molecular mechanisms of triptolide-induced anti-resistance and sensitization effects include change in enzymes and ABC transporters, induction of cell death pathways,increase of tumor suppressors and decrease of oncogenic factors, and interactions with the RNA polymerase II complex; besides, targeting to cancer stem cells and tumor-microenvironment-meiated resistance and alternations in epigenetics are also involved. This review summarizes the broad targeting of triptolide to resistance and sensitization for cancer therapy; its semi-synthetic derivatives and novel delivery systems which are developed to enhance the solubility and reduce the toxicity will also be discussed.
雷公藤甲素 肿瘤细胞 耐药机制 抗肿瘤作用
侯振彦 汤淮波 颜苗 张毕奎
中南大学湘雅二医院药学部,湖南 长沙 410011;中南大学临床药学研究所,湖南 长沙 410011 湘潭大学化学学院,湖南 湘潭 411105 中南大学湘雅二医院药学部,湖南 长沙 410011;中南大学临床药学研究所,湖南 长沙 410011;中南大学湘雅药学院,湖南 长沙 410013
国内会议
西安
中文
344-358
2017-11-04（万方平台首次上网日期，不代表论文的发表时间）