乌苏酸文献3遍.docVIP

乌苏酸抗肿瘤作用机制的研究进展 摘要：乌苏酸是存在于天然植物中的一种三萜类化合物EGFR/MAPK 通路途径 1.3通过抑制 FoxM1 转录因子的作用途径 1.4 对环氧化酶(COX-2)途径的影响 2. 抗血管生成 3.诱导肿瘤细胞凋亡 3.1乌苏酸诱导凋亡的半胱天冬氨酸酶 (Caspase) 途径和细胞色素C途径 3.2核因子-KB (NF-KB) 途径 3.3对肿瘤坏死因子相关凋亡诱导配体（TRAIL）途径的影响 3.4.对雷帕霉素靶蛋白bstract：Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid.In the past few years ,UA was found a wide anti-tumor function,and UA acted this function through many ways,such as inhibit tumor proliferation, anti-angiogenesis,induce tumor apoptosis,DNA protection, immunologic surveillance and inhibit tumor migration .And among these，the immunologic surveillance has not been involved before.This review summarizes previous and current information of UA, and provides new insights into the underlying mechanisms of its activities. 关键词：乌苏酸 抗肿瘤 Keyword: Ursolic acid (UA) anti-tumor 乌苏酸广泛存在于天然植物中的一种三萜类化合物，具有镇静、抗炎、抗菌、抗糖尿病、抗溃疡、降低血糖等多种生物学效应E RK调节着细胞的增殖、分化和存活，ERK和其信号途径在肿瘤侵袭和转移过程中起中介和放大信号的作用。在许多人类的癌症（如口腔癌、黑色素瘤 、乳腺癌等）中都可发现ERK的过度激活。[Calvo F, Agudo-Ibá?ez L, Crespo P.The Ras-ERK pathway: understanding site-specific signaling provides hope of new anti-tumor therapies. Bioessays. 2010 May;32(5):412-21.]乌苏酸可抑制ERK活性和p-ERK1/2表达，从而抑制人卵巢癌CAOV3细胞、HT-29结肠癌细胞增殖[Wang X, Li L, Wang B, Xiang J.Effects of ursolic acid on the proliferation and apoptosis of human ovarian cancer cells.] 1.2通过抑制 EGFR/MAPK 通路途径 MAPK的活化可能通过细胞过度增殖参与致癌过程。[Park KS, Kim NG, Kim JJ, et al. Differential regulation of MAP kinase cascade in human colorectal tumorigenesis[J]. Br J Cancer, 1999, 81(7):1116|1121.]MAPK有多个亚家族，其中较为确定的，在细胞功能中发挥重要作用的有细胞外信号调节激酶（ERK），c|Jun|N端激酶（JNK/SAPK）以及p38MAPK。近年来，较多研究发现MAPK信号通路与肿瘤恶性演进相关。[Yong HY, Koh MS, Moon A.The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer. Expert Opin Investig Drugs. 2009 Dec;18(12):1893-905.] 乌苏酸可促进HT-29 细胞的EGFR, ERK1/2, p38 ,MAPK, and JNK的磷酸化，通过抑制EGFR/MAPK通路，抑制 HT-29细胞增殖 [Shan JZ, Xuan YY, Zheng S, Dong Q, Zhang SZ.Ursolic acid inhibits proliferation and induces apoptosis of HT-29 colon cancer cells by inhibit