桦木酸抗肿瘤作用及机制的研究进展  

Anti-tumor Effect and Mechanism of Betulinic Acid:A Review

作　　者：王雪振 牟悦 郝倩 张亚楠[1] 夏雷[1] WANG Xue-zhen;MU Yue;HAO Qian;ZHANG Ya-nan;XIA Lei(Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]山东中医药大学,济南250355

出　　处：《中国实验方剂学杂志》2021年第21期223-231,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81703839);山东省研究生教育优质课程项目(SDYKC20055)。

摘　　要：桦木酸是一种桦树皮、黄芪、白芍、大枣、地榆、杜仲、甘草、木香、酸枣仁等多种草本植物中提取的羽扇豆烷型五环三萜类天然活性成分,其以低毒、高效、多功能特点备受医者关注。研究发现,桦木酸具有显著的抗肿瘤生物活性,有望成为治疗恶性肿瘤的潜在药物。迄今多项研究表明,桦木酸可通过多种机制途径对恶性肿瘤产生促进凋亡、抑制增殖、转移及侵袭、诱导细胞周期停滞等作用,且在卵巢癌、乳腺癌、胃癌、肺癌、结直肠癌、前列腺癌等多种恶性肿瘤中均观察到抗肿瘤功效,其抗肿瘤活性主要体现在通过调节抑癌基因p53,p21表达,触发活性氧(ROS)生成,下调核转录因子-κB(NF-κB)表达进而调节B细胞淋巴瘤-2(Bcl-2)家族引起肿瘤细胞产生凋亡,此外还可通过调节转录因子(Sp1/3/4)诱导细胞凋亡;其抗增殖活性主要体现在对周期蛋白(cyclin B,cyclin D),周期蛋白依赖性激酶(CDK,CDC)等蛋白的调节作用;其抑制转移侵袭功能主要通过调节基质金属蛋白酶(MMP),基质金属蛋白酶抑制物(TIMP),通过上调钙黏蛋白E(E-cadherin),下调N-钙黏蛋白(N-cadherin),阻断上皮-间质转化(EMT)进程等途径实现,此外桦木酸还可通过阻滞细胞周期、影响肿瘤代谢重编程、诱导肿瘤细胞自噬等发挥其抗肿瘤作用。虽桦木酸在抗肿瘤方面研究数量较多,功效作用强,但缺乏对桦木酸抗肿瘤作用的系统性综述,为此,该文基于桦木酸抗肿瘤作用机制途径进行文献综述,以期为研究者提供信息参考。Betulinic acid(BA)is a lupane pentacyclic triterpene extracted from a variety of Chinese herbs such as Betulae Platyphyllae Cortex,Astragali Radix,Paeoniae Radix Alba,Jujubae Fructus,Sanguisorbae Radix,Eucommiae Cortex,Glycrrhizae Radix et Rhizoma,Aucklandiae Radix,and Ziziphi Spinosae Semen.It has attracted wide attention from doctors because of its low toxicity,high efficacy,and multiple functions.BA has been found to possess a significant anti-tumor biological activity,and it is expected to become a potential drug for the treatment of malignant tumors.So far,a number of studies have shown that BA is able to promote apoptosis,inhibit proliferation,metastasis and invasion,and induce cell cycle arrest via multiple mechanisms,thus resisting various malignant tumors such as ovarian cancer,breast cancer,gastric cancer,lung cancer,colorectal cancer,and prostate cancer.It exerts the anti-tomor effect by regulating the expression of cancer suppressor genes p53 and p21,triggering the generatoipn of reactive oxygen species(ROS),down-regulating the expression of nuclear transcription factor-κB(NF-κB),adjusting the B lymphocytoma-2(Bcl-2)family to cause tumor cell apoptosis,and regulating transcription factor Sp1/3/4 to induce apoptosis.Its anti-proliferative activity is mainly achieved via the regulation of cyclin B,cyclin D and cyclin dependent kinases CDK and CDC.Its efficacy in inhibiting metastasis and invasion is mainly realized by regulating matrix metalloproteinase(MMP)and matrix metalloproteinase inhibitor(TIMP),up-regulating E-cadherin,down-regulating N-cadherin and blocking the epithelial-mesenchymal transformation(EMT).In addition,BA also induces cell cycle arrest,affects tumor metabolic reprogramming,and activates autophagy to inhibit tumor.Although there are a large number of studies on BA against tumors and its efficacy has been proved strong,the systematic review on its anti-tumor effect is still lacking.Therefore,this study reviewed the antitumor effect and mechanism of BA,in order to provide reference f

关 键 词：桦木酸 肿瘤 癌症 机制 研究进展 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学]