Guttiferone K抑制胰腺癌的体内外活性研究  

The Activity Study of Pancreatic Cancer Inhibited by Guttiferone K both in vitro and in vivo

作　　者：陈小琼[1,2] 李洋[1,2] 张伊婧 吴蓉[1,2] 席志超[1,2] 谭红胜[1,2] 

机构地区：[1]上海中医药大学中药学院,上海201203 [2]中药创新药物研发上海高校工程研究中心,上海201203

出　　处：《世界科学技术-中医药现代化》2017年第2期241-246,共6页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：中国博士后科学基金会第60批中国博士后科学基金面上项目(2016M601641):藤黄属PPAPs类化合物抑制前列腺癌复发的活性研究;负责人:席志超

摘　　要：目的:本文主要探讨从藤黄属植物云南藤黄Garcinia yunnanensis中提取分离得到的化合物Guttiferone K(GUTK)抑制人胰腺癌增殖的体内外作用。方法:用MTT法检测GUTK对5株人胰腺癌细胞增殖的抑制作用;利用免疫印迹法检测凋亡相关蛋白Caspase-3、多聚二磷酸腺苷核糖聚合酶(Poly Adenosinediphosphate-Ribose Polymerase,PARP)和Bcl-x L蛋白水平的变化;将人胰腺癌细胞MIA Pa Ca-2接种到裸鼠胰腺上,腹腔注射GUTK进行干预,隔天给药,4周后摘取小鼠胰腺肿瘤并检测瘤体积和瘤重;通过免疫组化法检测cleaved Caspase-3在各组肿瘤组织中表达水平的差异。结果:GUTK在低浓度时能有效抑制5种人胰腺癌细胞的增殖;GUTK呈时间及剂量依赖地诱导Caspase-3和PARP剪切,并下调Bcl-x L的表达;体内实验表明GUTK能显著抑制胰腺癌裸鼠原位移植瘤的生长,并诱导cleaved Caspase-3在肿瘤组织中的表达。结论:GUTK在体内外均能诱导胰腺癌细胞的凋亡,具有潜在的抗胰腺癌作用,有望开发成治疗胰腺癌的药物。This study aimed at exploring the effects of Guttiferone K（GUTK）, a compound isolated from G. yunnanensis,on inhibiting the proliferation of pancreatic cancer cells both in vitro and in vivo. MTT assay was used to detect theinhibitory effects of GUTK on the proliferation of five human pancreatic cancer cell lines. Western blot was adopted todetect the apoptosis-related protein expressions of Caspase-3, poly adenosinediphosphate-ribose polymerase（PARP）and Bcl-x L. For in vivo study, the human pancreatic cancer cell MIA Pa Ca-2 was orthotopically injected into thepancreatic tail of the orthotopic mice. One week later, GUTK was administered by intraperitoneal（i.p.） injection everyother day for 4 weeks. The volume and weight of the tumor tissue were measured. The protein expression level of cleavedcaspase-3 in tumor tissue of all the groups was quantified by immunohistochemistry. As a result, it was found that GUTKeffectively inhibited the proliferation of the five human pancreatic cancer cell lines at a low concentration. GUTKinduced caspase-related apoptosis by triggering a series of events in MIA Pa Ca-2 cells including cleaved Caspase-3 andPARP activation, Bcl-x L down-regulation, and eventually cell death in a time and dose dependent manner. Furthermore,in vivo study revealed that intraperitoneal injection of GUTK significantly suppressed the growth of pancreatic cancercells in the orthotopic mouse models, and the protein level of cleaved caspase-3 was increased in the GUTK andgemcitabine treated groups. It was concluded that GUTK induced apoptosis in human pancreatic cancer both in vitro and in vivo, and was potential to develop into a clinical anticancer agent.

关 键 词：云南藤黄 Guttiferone K 胰腺癌 凋亡 

分 类 号：R28[医药卫生—中药学]