MMP2 在胃癌侵袭和转移中的作用
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1. 延安大学医学院,陕西 延安 716000; 2. 空军军医大学实验动物中心,西安 710032

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Role of matrix metalloproteinase-2 in the invasion and metastasis of gastric cancer
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1. Medical College of Yan’an University, Yan’an 716000, China. 2. Laboratory Animal Center, the Air Force Medical University, Xi’an 710032

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    摘要:

    目的 探索 MMP2 在胃癌侵袭和转移中的作用,以期为胃癌转移提供新的预测指标及治疗靶点。 方法 选择胃癌细胞系 MKN-1 转染慢病毒,使 MMP2 低表达,获得细胞系 sh-MMP2,并通过 RT-PCR 及 Western Blot 检测转染后 MKN-1 细胞中 MMP2 表达情况。 进一步通过细胞划痕实验、Transwell、CCK8 实验分别检测 MMP2 低表达后细胞迁移能力、侵袭能力、增殖能力变化。 利用裸鼠建立 sh-MMP2 细胞系异种移植模型及转移模型,观察 MMP2 低表达后体内肿瘤生长变化及体内转移能力变化。 通过 RT-PCR 及 Western Blot 检测 MMP2 对 EMT 及细胞凋亡的影响。 结果 MMP2 低表达后胃癌细胞迁移能力(P< 0. 05)、侵袭能力(P< 0. 01)、增殖能力(P< 0. 05)均下降。 体内实验结果显示 MMP2 低表达可显著减缓肿瘤生长及体内转移( P< 0. 01)。 进一步实验表明降低 MMP2 的表达,可抑制细胞 EMT 过程并增加细胞凋亡。 结论 MMP2 低表达可通过抑制 EMT 过程及增加细胞凋亡,减弱胃肿瘤细胞迁移能力、侵袭能力和增殖能力,抑制胃癌的发展。

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    Objective To explore the role of matrix metalloproteinase-2 (MMP2) in gastric cancer invasion and metastasis, so as to provide a new predictive index and therapeutic target for gastric cancer metastasis. Methods Gastric cancer cell line MKN-1 was transfected with lentivirus to make a cell line with low expression of MMP2, denoted sh-MMP2. Real-time PCR and Western Blot were used to detect MMP2 expression in MKN-1 cells after transfection. Cell scratch, Transwell and CCK8 assays were used to detect changes in migration, invasion and proliferation, respectively, of MKN-1 cells. Xenotransplantation and metastasis models of MKN-1 NC and MKN-1 sh-MMP2 cell lines were established in nude mice, and changes in tumor growth and metastasis were observed in vivo. The effects of MMP2 on apoptosis and epithelial- to-mesenchymal transition ( EMT) were detected by Real-time PCR and Western Blot. Results The migration ( P< 0.05), invasion (P< 0.01) and proliferation ( P< 0.05) of gastric cancer MKN-1 cells were decreased with the reduction of MMP2 expression. In vivo result showed that low expression of MMP2 significantly slowed down tumor growth and metastasis (P< 0.01). Further experiments demonstrated that decreasing MMP2 expression in gastric cancer cells increased apoptosis and inhibited the EMT process. Conclusions Low expression of MMP2 can retard the development of gastric cancer by increasing cell apoptosis and inhibiting the EMT process, as well as reducing the migration, invasion and proliferation of gastric cancer cells.

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毛玉宁,柳森森,巩淼淼,赵菊梅,师长宏. MMP2 在胃癌侵袭和转移中的作用[J].中国实验动物学报,2022,30(1):23~30.

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  • 收稿日期:2021-06-28
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  • 在线发布日期: 2022-04-14
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