异甘草素抗肿瘤活性及初步机制研究  

Antitumor activities and mechanisms of isoliquiritigenin

作　　者：王志强[1,2] 张秀英[3] 李文广[1] 黄双盛[4] 刘圆圆[1] 胡腊梅[1] 侯翠兰[1] 张小郁[1] 

机构地区：[1]兰州大学基础医学院 [2]甘肃省妇幼保健院生殖医学中心 [3]甘肃省人民医院急诊科 [4]西北民族大学医学院,甘肃兰州730000

出　　处：《中国药理学通报》2015年第8期1159-1165,共7页Chinese Pharmacological Bulletin

基　　金：甘肃省自然科学研究基金计划项目(No 1208RJZA231)

摘　　要：目的探讨异甘草素(isoliquiritigenin,ISL)抗肿瘤活性及初步机制。方法采用SRB法检测ISL对A549、SW620和HMEC-1细胞增殖的抑制作用;Transwell小室检测ISL对HMEC-1细胞迁移能力的影响;明胶酶谱法检测ISL对HMEC-1细胞MMP-2和MMP-9的表达;管样结构形成实验测定ISL对HMEC-1细胞管样结构形成能力;细胞内活性氧(ROS)通过荧光探针DCFH-DA进行测定;流式细胞术检测ISL对HMEC-1的细胞周期。鸡胚绒毛尿囊膜血管生成实验检测ISL体内抗血管生成作用。结果 ISL可明显抑制A549、SW620和HMEC-1细胞的增殖、HMEC-1细胞的迁移、管样结构形成以及细胞内MMP-2和MMP-9的表达,且均呈现浓度依赖关系。同时,ISL还可抑制HMEC-1细胞内由VEGF诱导产生的ROS量,且存在浓度依赖关系。流式细胞术检测发现高浓度ISL可将HMEC-1细胞阻滞于S期,而低浓度ISL通过诱导细胞凋亡来抑制HMEC-1细胞的增殖。ISL能明显抑制鸡胚尿囊膜新生毛细血管的生成。结论ISL具有明显的抗肿瘤活性,能抑制血管生成,其机制可能与清除HMEC-1细胞内ROS生成,诱导细胞凋亡有关。Aim To investigate the effects of isoliquiri- tigenin （ISL） on anti-angiogenesis both in vitro and in vivo and its mechanisms. Methods We assessed the antiangiogenic activities of ISL on proliferation viabili- ty, migration and tube formation of human microvascu- lar endothelial cell line-1 （ HMEC-1 ） in vitro. The cell proliferation viability was assessed using the Sulforho- damine B （ SRB ） assay. Modified Boyden Transwell chamber assay was clone to study the effect of ISL on HMEC-1 cells migration. 2＇, 7＇-dichlorofluorescein all- acetate （DCFH-DA） was used to measure the levels of intraeellular reactive oxygen species （ ROS ）, which was induced by VEGF. Metalloproteinase-2 （MMP-2）and metaUoproteinase-9 （ MMP-9 ） expressions by HMEC-1 cells were assessed through gelatin zymogra- phy assay. HMEC-1 cells cycle was detected by flow cytometry. Moreover, we investigated the in vivo anti- angiogenic activity of ISL on chicken embryos nap al- lantoic membrane model （CAM）. Results ISL con- centration-dependently inhibited the growth of HMEC-1 cells as well as SW620 and A549 cells. ISL signifi- cantly and concentration-dependently suppressed the migration activity of HMEC-1 cells. Tube sample struc- ture formation further confirmed the effect of ISL on an- ti-angiogenesis. Moreover, lular ROS level, MMP-2 ISL also inhibited intracel- and MMP-9 expression byHMEC-1 cells. ISL induced endothelial cell apoptosis at a low concentration （ISL 12.5 μmol · L-1） and blocked the cells in s phase of mitosis at higher con- centrations （ISL 25 - 100 μmol ·L-1 ）. Furthermore, ISL distinctly inhibited the angiogenesis of chick em- bryos in vivo. Conclusions ISL has anti-tumor andangiogenesis effects on HMEC-1 cells. The mechanism may be related to intracellular ROS scavenging and ap- optosis induction of HMEC-1 cells.

关 键 词：异甘草素 抗肿瘤 血管生成 人微血管内皮细胞 血管内皮生长因子 细胞凋亡 

分 类 号：R284.1[医药卫生—中药学] R329.24[医药卫生—中医学]