MMP2在胃癌侵袭和转移中的作用

Role of matrix metalloproteinase-2 in the invasion and metastasis of gastric cancer

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。

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 epithelialto-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.