南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (3): 438-442.doi: 10.12122/j.issn.1673-4254.2022.03.18

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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

葛 钰，卢林明，田澍雨，肖 雨，谢尚富，王 琪，支 慧   

  1. 皖南医学院病理解剖教研室，安徽 芜湖 241002
  • 出版日期:2022-03-20 发布日期:2022-04-11

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

GE Yu, LU Linming, TIAN Shuyu, XIAO Yu, XIE Shangfu, WANG Qi, ZHI Hui   

  1. Department of Pathology, Wannan Medical College, Wuhu 241002, China
  • Online:2022-03-20 Published:2022-04-11

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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、20 μg/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Westernblot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。

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

Abstract: 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.

Key words: agkistrodon halys venom antitumor component-I; triple-negative breast cancer; vasculogenic mimicry; matrix metalloproteinase-2