皖南蝮蛇毒抑瘤组分-Ⅰ通过MMP2抑制三阴性乳腺癌细胞体外血管生成拟态  

Agkistrodon halys venom antitumor component-Ⅰ inhibits vasculogenic mimicry in triple-negative breast cancer cells in vitro by down-regulating MMP2

作　　者：葛钰 卢林明[1] 田澍雨 肖雨 谢尚富 王琪 支慧 GE Yu;LU Linming;TIAN Shuyu;XIAO Yu;XIE Shangfu;WANG Qi;ZHI Hui(Department of Pathology,Wannan Medical College,Wuhu 241002,China)

机构地区：[1]皖南医学院病理解剖教研室,安徽芜湖241002

出　　处：《南方医科大学学报》2022年第3期438-442,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(21906122);安徽省大创基金项目(S201910368014)。

摘　　要：目的 探讨皖南蝮蛇毒抑瘤组分-Ⅰ(AHVAC-Ⅰ)对三阴性乳腺癌细胞MDA-MB-231血管拟态能力的影响及其可能的作用机制。方法 采用CCK8实验根据半数抑制浓度(IC50)确定AHVAC-Ⅰ实验浓度,将MDA-MB-231细胞分为3组:对照组(不含药物的培养基处理)、AHVAC-Ⅰ实验组、药物对照组(5-Fu处理)。Matrigel实验检测分析不同浓度AHVAC-Ⅰ作用对MDA-MB-231血管拟态能力的影响。运用定量PCR和Western blot检测基质金属蛋白酶2(MMP2)与MMP9的表达水平。结果 相较对照组,5、10、20μg/mL AHVAC-Ⅰ可显著抑制MDA-MB-231细胞的血管拟态能力(P<0.01),且呈剂量依懒性。RT-PCR及Western blot结果显示,AHVAC-Ⅰ能够抑制MMP2的表达水平,降低三阴性乳腺癌细胞MDA-MB-231分泌生成的MMP2(P<0.01),而MMP2的补入可恢复因AHVAC-Ⅰ作用而抑制的MDA-MB-231细胞血管拟态的能力。结论 AHVAC-Ⅰ可通过下调MMP2的表达,抑制乳腺癌细胞MDA-MB-231血管生成拟态的形成能力。Objective To investigate the inhibitory effect of agkistrodon halys venom antitumor component-Ⅰ(AHVAC-Ⅰ) on vasculogenic mimicry(VM) formation in triple-negative breast cancer MDA-MB-231 cells and explore its possible mechanism.Methods CCK8 assay was used to determine the optimal concentration of AHVAC-Ⅰ for cell treatment based on its halfinhibitory concentration(IC50). MDA-MB-231 cells were treated with different concentrations of AHVAC-Ⅰ or 5-Fu, and the changes in vasomimetic capacity of the cells were examined using Matrigel assay. The expression levels of matrix metalloproteinase-2(MMP2) and MMP9 in the treated cells were detected using quantitative PCR and Western blotting.Results Compared with the control treatment with culture medium, treatment with 5, 10 and 20 μg/mL AHVAC-Ⅰ significantly reduced vasomimetic ability of MDA-MB-231 cells in a dose-dependent manner(P<0.01). MMP2 supplementation obviously restored the vasomimetic ability of the cells inhibited by AHVAC-Ⅰ. Conclusion AHVAC-Ⅰ inhibits VM formation in triplenegative breast cancer cells in vitro by down-regulating MMP2 production.

关 键 词：皖南蝮蛇毒抑瘤组分-Ⅰ 三阴性乳腺癌 血管拟态 基质金属蛋白酶2 

分 类 号：R285[医药卫生—中药学]