雷公藤内酯的抗肿瘤作用机制

Antitumor effect and mechanism of Triptolide

雷公藤内酯(Triptolide,TPL)是卫矛科植物雷公藤(Tripterygium wilfordii Hook. f)的主要生物活性成分,抑制细胞增殖,诱导细胞凋亡,抑制肿瘤转移并增强其他化疗药物的敏感性。TPL通过影响多种分子和信号通路,如半胱氨酸蛋白酶,热休克蛋白,NF-κB和DNA修复相关因子等,发挥抗癌作用。低剂量TPL作为辅助治疗剂,能够降低患者对目前化疗药物所产生的抗药性,提高TPL和化疗药物的抗癌效果减轻毒性。TPL诱导的低抗药性和敏化作用的分子机制包括细胞凋亡途径的诱导,肿瘤抑制因子的增加和致癌因子的减少,与RNA聚合酶II复合物的相互作用,及靶向肿瘤干细胞和肿瘤微环境介导的抗性。本综述总结了有关TPL在肿瘤治疗方面目前现有的研究新进展,特别是肿瘤治疗中的靶点和分子机制,并对肿瘤细胞的作用机制进行了较为深入的概括。

Triptolide(TPL) is the main bioactive component of Tripterygium wilfordii Hook. f., inhibits cell proliferation, induces apoptosis, inhibits tumor metastasis and enhances the sensitivity of other chemotherapeutic drugs. TPL exerts anticancer effects by affecting a variety of molecules and signaling pathways, such as cysteine proteases, heat shock proteins, NF-κB and DNA repair-related factors. As adjunctive therapeutic agent, low-dose TPL can reduce the drug resistance of patients with current chemotherapy drugs, and improve the anti-cancer effect of TPL and chemotherapy drugs to reduce toxicity. Molecular mechanisms of TPL-induced low drug resistance and sensitization include induction of apoptosis pathways, increase in tumor suppressor factors and reduction of oncogenic factors, interaction with RNA polymerase II complexes, and targeting of cancer stem cells and tumors microenvironment-mediated resistance. This review summarizes recent advances in TPL’s current research in cancer therapy, particularly in tumor therapy, and provides a more in-depth summary of the mechanisms of action of tumor cells.