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蛇毒半胱氨酸蛋白酶抑制剂重组蛋白对小鼠黑色素瘤血管生成拟态的影响及其机制 预览 被引量:6

Effect of recombinant snake venom cystatin on mouse melanoma vasculogenic mimicry and its underlying mechanisms
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摘要 目的 探讨蛇毒半胱氨酸蛋白酶抑制剂(snake venom cystatin,sv-cystatin)重组蛋白对小鼠黑色素瘤血管生成拟态(vasculogenic mimicry,VM)形成的影响及相关机制.方法建立Matrigel胶肿瘤细胞类血管生成模型,分析sv-cystatin重组蛋白(10、25、50、100、200mg/L)对B16F10细胞VM形成及基质金属蛋白酶-2、9[matrix metalloproteinase-2(MMP-2)、MMP-9]蛋白表达的影响;建立C57BL/6小鼠黑色素瘤实验性肺转移模型,经25、50mg/kg重组蛋白治疗后,应用CD34和过碘酸雪夫(periodic acid-schiff stain,PAS)双重染色法检测肺转移瘤VM形成,免疫组织化学法检测转移瘤MMP-2、MMP-9表达.结果 与对照组相比,sv-cystatin重组蛋白作用后B16F10细胞体外VM形成及MMP-2、MMP-9蛋白表达明显减少,并呈剂量依赖性(P〈0.05);两治疗组小鼠肺转移瘤VM形成及MMP-2、MMP-9表达明显下降(P〈0.05).结论 sv-cystatin重组蛋白能够抑制VM形成;下调MMP-2、MMP-9表达是其中的机制之一. Objective To investigate the effect of recombinant snake venom cystatin (sv-cystatin) on vasculogenic mimicry (VM) formation of mouse melanoma in vitro and in vivo and the mechanisms underlying this effect. Methods The effect of recombinant sv-cystatin (10, 25, 50, 100 and 200 mg/L) on VM of mouse melanoma cell B16F10 in vitro was observed by tube-like structure formation. Experimental lung metastasis assay was used to analyze the effect of sv-cystatin (three intravenous injections of 25 or 50 mg/kg) on VM in surface metastatic lesions by CD34 and periodic acid-Schiff (PAS) double staining. Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions in B16F10 cells were assessed by immunocytochemistry in vitro and immunohistochemistry in vivo, respectively. Results The number of VM and the expressions of MMP-2 and MMP-9 were decreased significantly in dose-dependent manner after treatment with an increased dose of recombinant sv-cystatin compared to those in control group (P (0. 05). In vivo, recombinant sv-cystatin administration significantly suppressed lung tumor colonies, VM formation as well as MMP-2 and MMP-9 expressions in C57BL/6 mice (P〈0.05). Conclusion Recombinant sv-cystatin can inhibit VM formation of B16F10 cells via down-regulating the expressions of MMP-2 and MMP-9.
作者 谢群 林扬元 林丽琳 翁剑武 林建银 XIE Qun,LIN Yang-yuan,LIN Li-lin,WENG Jian-wu,LIN Jian-yin Key Laboratory of Ministry of Education for Gastrointestinal Cancer/Research Center of Molecular Medicine, Fujian Medical University, Fuzhou 350004~ 2. School of Basic Medical Science, Putian College, Putian 351100, China)
出处 《西安交通大学学报:医学版》 CAS CSCD 北大核心 2014年第2期169-174,共6页 Journal of Xi‘an Jiaotong University:Medical Sciences
基金 国家自然科学基金资助项目(No.30371747) 福建省科技重大资助项目(No.2002Y003) 福建省自然科学基金指导性科技计划项目(No.2012D117)
关键词 蛇毒 半胱氨酸蛋白酶抑制剂 血管生成拟态 黑色素瘤 基质金属蛋白酶-2 基质金属蛋白酶-9 snake venom cystatin vasculogenic mimicry (VM) melanoma matrix metalloproteinase-2(MMP-2) matrix metalloproteinase-9 (MMP-9)
作者简介 谢群(1974-),女(汉族),博士,副教授. 研究方向:肿瘤的复发与转移. E-mail: xqptu@163.com
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参考文献13

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