摘要
雷公藤内酯醇(TPL)是目前从传统中药雷公藤中分离出活性最高的化学成分,具有高效的抗炎、抗生育、抗类风湿、免疫调节等作用,近年来发现TPL还具有高效、广谱的抗肿瘤活性,且其抗肿瘤机制已成为国内外研究热点。目前化疗是肿瘤的主要疗法,但肿瘤细胞产生的多药耐药(MDR)常使化疗难以取得良好效果,且肿瘤多药耐药机制十分复杂,因此寻找高效低毒的MDR逆转剂显得尤为重要。文献检索发现肿瘤MDR机制主要包括多药耐药蛋白引起的多药耐药,调控基因介导的多药耐药,酶介导的多药耐药3个方面,以及肿瘤细胞内p H改变,药代动力学改变等。TPL不仅能协同增强多种化疗药物的抗肿瘤效应,还可逆转肿瘤多药耐药,TPL针对肿瘤MDR的逆转机制主要涉及下调MDR1/P-糖化蛋白(P-gp)的表达,抑制蛋白激酶B/核转录因子-κB(Akt/NF-κB)的活性,提高细胞内活性氧(ROS)水平,诱导细胞凋亡,抑制多药耐药相关蛋白(MRP)表达,调节促凋亡基因/抗凋亡基因(Bax/Bcl-2)表达,抑制Bcr/abl融合基因T315I点突变7个方面。现从肿瘤多药耐药机制及TPL逆转多药耐药机制两方面作一概述,为逆转肿瘤多药耐药提供新思路。
Triptolide（ TPL） is the most active chemical constituents derived from the traditional Chinese medicine Tripterygium wilfordii so far. It has the effect of anti-inflammation,anti-fertility,anti-rheumatism and immune regulation. In recent years,it has been found that TPL also has high efficiency and broad spectrum antitumor activity, and its anti-tumor mechanism has become a hot spot at home and abroad. At present,chemotherapy is the main therapy for tumor. However,the multi-drug resistance（ MDR） caused by tumor cells also makes it difficult to achieve good results. In addition,the mechanism of tumor multi-drug resistance is very complex,so it is important to find the MDR reversal agent with high efficiency and low toxicity. In the literature search,it is found that the mechanism of MDR in the tumor mainly includes multi-drug resistance caused by multidrug resistance protein, multi-drug resistance mediated by regulatory genes（ including anti-apoptosis related signaling pathway and apoptosis-related genes and proteins）,and multi-drug resistance mediated by enzymes,as well as the changes of p H in tumor cells,and pharmacokinetic changes. The latest research shows that TPL can not only enhance the anti-tumor effect of a variety of chemotherapy drugs, but also can reverse the multi-drug resistance of tumor. However, its reversal mechanism has not been widely studied at home and abroad. The reversal mechanism of TPL in MDR is mainly related to down-regulating MDR1/P-gp expression,inhibiting Akt/nuclear factor（ NF）-κB activity,increasing reactive oxygen specise（ ROS） level in cells,inducing apoptosis,inhibiting multidrug resistance-associated protein（ MRP） expression, regulating Bax/Bcl-2 expression and inhibiting mutation of Bcr/abl fusion gene T315 I. In this paper,an overview would be written from the mechanism of tumor multi-drug resistance and TPL＇s reversal mechanism of multi-drug resistance,to provide new ideas for the reversal of tumor multi-drug resistance and benefit various patients.
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2016年第10期229-234,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
山东省自然科学基金项目(ZR2014HP022)
关键词
雷公藤内酯醇
肿瘤
逆转
多药耐药
triptolide
tumor
reversal
multiple drug resistance
