Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410011, China; Institute of Clinical Pharmacy, Central South University, Changsha 410011, China.
Molecular Science and Biomedicine Laboratory, College of Life Sciences, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, Hunan University, Changsha 410082, China.
Biomed Pharmacother. 2018 Aug;104:771-780. doi: 10.1016/j.biopha.2018.05.088. Epub 2018 May 29.
Cancer cell resistance to current anticancer therapeutics as well as the side effects are still obstacles to successful cancer therapy. Hence, the development of novel anticancer agents or therapeutics is of vital significance, and especially rational adjuvant therapies containing low-cost natural products with multiple targets have attracted great interests. Triptolide, the main biocomponent of Tripterygium wilfordii Hook F, is restricted in clinical applications mainly due to its severe systemic toxicities, although it has shown strong antitumor activities in preclinical studies. Mounting evidence suggests that 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. Furthermore, several unique antitumor targets of triptolide make it superior to other therapeutics. The molecular mechanisms of triptolide-induced anti-resistance and sensitization effects include changes in ATP-binding cassette transporters, induction of apoptosis pathways, increase in tumor suppressors and decrease in oncogenic factors, and interactions with the RNA polymerase II complex; targeting cancer stem cells and tumor-microenvironment-mediated resistance are also involved. Besides, some synthetic derivatives and novel delivery systems of triptolide are also developed to enhance the water-solubility and reduce the toxicity, which will also be discussed.
癌症细胞对当前抗癌疗法的耐药性以及副作用仍然是癌症治疗成功的障碍。因此，开发新型抗癌药物或疗法至关重要，特别是含有多种靶点的低成本天然产物的合理辅助疗法引起了极大的兴趣。雷公藤红素是雷公藤 Hook F 的主要生物成分，尽管在临床前研究中显示出很强的抗肿瘤活性，但由于其严重的全身毒性，在临床应用中受到限制。越来越多的证据表明，低剂量的雷公藤红素作为辅助治疗剂可以规避对当前抗癌疗法的耐药性，增强抗癌效果，并减轻雷公藤红素和抗癌疗法的毒性。此外，雷公藤红素的几个独特的抗肿瘤靶标使其优于其他疗法。雷公藤红素诱导抗耐药和增敏作用的分子机制包括改变 ATP 结合盒转运蛋白、诱导细胞凋亡途径、增加肿瘤抑制因子和减少致癌因子，以及与 RNA 聚合酶 II 复合物的相互作用；还涉及针对癌症干细胞和肿瘤微环境介导的耐药性。此外，还开发了一些雷公藤红素的合成衍生物和新型递药系统，以提高水溶性和降低毒性，这也将进行讨论。
