基质金属蛋白酶-11在骨肉瘤中的表达及生物学功能研究

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摘要目的检测基质金属蛋白酶-11(matrix met alloproteinase-11，MMP-11)在骨肉瘤组织及癌旁组织中的表达特征，并观察敲低其表达对骨肉瘤细胞生物学行为的影响。方法采用荧光定量PCR(Quantitative RT-PCR)和免疫组化染色技术检测40例骨肉瘤及癌旁组织中MMP-11的表达特征。体外试验采用骨肉瘤细胞系(HOS和Saos-2)转染MMP-11 siRNA(试验组)和siRNA control(阴性对照组)，48h后收集细胞，提取RNA和蛋白质，通过荧光定量PCR和蛋白质印迹观察两组细胞中MMP-11的表达变化；同时采用四甲基偶氮唑盐微量酶反应比色法(3-(4，5-dimethyl-2-thiazolyl)-2，5-diphenyl-2-H-tetrazolium bromide，MTT)、细胞划痕试验以及流式细胞术探究敲低MMP-11表达对骨肉瘤细胞增殖、迁移及凋亡的影响。结果骨肉瘤组织中MMP-11 mRNA的表达量较癌旁组织明显升高，癌旁组织中MMP-11 mRNA的表达量为(1.0±0.22)，则其在骨肉瘤组织中相对表达量为(3.94±0.79)(P＜0.05)。免疫组化染色技术亦显示MMP-11蛋白在骨肉瘤组织的阳性率显著高于癌旁组织(P＜0.05)。骨肉瘤细胞中转染MMP-11 siRNA可显著降低细胞内源性MMP-11表达水平(P＜0.05)。敲低MMP-11的表达可显著抑制HOS和Saos-2细胞的增殖及迁移能力，并增加细胞凋亡(P＜0.05)。结论 MMP-11在骨肉瘤中呈现高表达状态，敲低其表达可抑制骨肉瘤细胞增殖、迁移并增加细胞凋亡，提示MMP-11在骨肉瘤的发生和发展过程发挥促癌作用。

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关键词 ：骨肉瘤, 基质金属蛋白酶-11, 升高, 增殖, 迁移, 凋亡

Abstract：Objective To detect the expression of matrix met alloproteinases 11 (MMP-11) in osteosarcoma tissues and adjacent matched normal osteosarcoma tissues，and explore the effect of silencing MMP-11 expression on the biological behaviors of osteosarcoma cells.Methods MMP-11 expression was detected in 40 paired osteosarcoma tissues and adjacent matched normal osteosarcoma tissues using Quantitative RT-PCR analysis and immunohistochemistry technology.MMP-11 siRNA and siRNA control were transfected into osteosarcoma cells (HOS and Saos-2).RNA and protein were collected after 48 h，and Quantitative RT-PCR analysis and Western blots were applied to detected the expression of MMP-11 in osteosarcoma cells.3-(4，5-dimethyl-2-thiazolyl)-2，5-diphenyl-2-H-tetrazolium bromide (MTT)，wound-healing assay and flow cytometry were applied to detected the growth，migration and apoptosis of osteosarcoma cells after RNAi-mediated silencing of MMP-11，respectively.Results The MMP-11 mRNA expression in osteosarcoma tissues was significantly up regulated than adjacent matched normal osteosarcoma tissues (P＜0.05).The mRNA expression levels of MMP-11 in the adjacent matched normal osteosarcoma tissues was (1.0±0.22)，while its relative expression in osteosarcoma tissues was (3.94±0.79)(P＜0.05).Immunohistochemical technique also showed that the positive rate of MMP-11 protein in osteosarcoma was significantly higher than that of in the adjacent matched normal osteosarcoma tissues (P＜0.05).Transfection of MMP-11 siRNA in osteosarcoma cells significantly reduced the expression levels of MMP-11 (P＜0.05).Knockdown of MMP-11 markedly inhibited cell growth and migration，and promoted cell apoptosis (P＜0.05).Conclusion MMP-11 is high expression in osteosarcoma.Knockdown of MMP-11 inhibits cell proliferation and migration，and induces cell apoptosis in osteosarcoma cells，suggesting MMP-11 acts as an oncogene involved in the development of osteosarcoma.

Key words： osteosarcoma matrix met alloproteinase-11 high expression proliferation migration apoptosis

基金资助:新疆维吾尔自治区自然科学基金(2017D01C128)

通讯作者: 王浩

作者简介: 缪晓刚(1976－ )，男，副主任医师，新疆维吾尔自治区人民医院骨科中心创伤病区，830001。

引用本文:

缪晓刚，阿布都艾尼·热吾提，王利，瓦热斯江·尼亚孜，郭子刚，王浩 *. 基质金属蛋白酶-11在骨肉瘤中的表达及生物学功能研究[J]. 实用骨科杂志, 2018, 24(11): 1002-1005.
Miu Xiaogang，Abuduaini Rewuti，Wang Li，et al. Study on Expression and Biological Function of Matrix Met alloproteinases 11 in Osteosarcoma. sygkzz, 2018, 24(11): 1002-1005.

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http://www.sygkzz.com/CN/ 或 http://www.sygkzz.com/CN/Y2018/V24/I11/1002

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