Department of Radiotherapy, The First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215006, P.R. China.
Department of Gastroenterology, Zhejiang Hospital, Hangzhou, Zhejiang 310000, P.R. China.
Mol Med Rep. 2019 Apr;19(4):2519-2526. doi: 10.3892/mmr.2019.9918. Epub 2019 Jan 31.
The present study aimed to explore the possible effects of membrane‑type 1 matrix metalloproteinase (MT1‑MMP) on gastric carcinoma cells proliferation and invasion. Immunohistochemistry analysis was conducted to measure MT1‑MMP expression level in 15 patients with gastric carcinoma. Subsequently, recombinant short hairpin RNA (shRNA) vectors targeting MT1‑MMP were constructed to silence the expression of MT1‑MMP in gastric carcinoma cells. Then, the inhibitive efficiency was verified via reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. The effects of MT1‑MMP silencing on cell proliferation and invasion were detected through Cell Counting Kit‑8 test and Transwell assays. The expression levels of vimentin and epithelial cadherin (E‑cadherin) were detected by RT‑qPCR. The immunohistochemistry analysis results revealed that MT1‑MMP expression in gastric carcinoma tissues was markedly overexpressed compared with non‑cancerous adjacent tissues. The MT1‑MMP expression level in cancer‑derived cell line AGS cells was also significantly increased compared with that in non‑cancer‑derived GES‑1 cells. In addition, the MT1‑MMP expression level in AGS cells was significantly decreased via shRNA transfection. Cell proliferation and invasion were markedly inhibited following knockdown of MT1‑MMP level in AGS cells. These inhibitory effects were associated with the decreased expression of vimentin and increased expression of E‑cadherin. MT1‑MMP was overexpressed in gastric carcinoma cells, and silencing of MT1‑MMP inhibited the proliferation and invasion of cells via regulating the expression of vimentin and E‑cadherin.
本研究旨在探讨膜型 1 基质金属蛋白酶（MT1-MMP）对胃癌细胞增殖和侵袭的可能影响。采用免疫组织化学分析检测 15 例胃癌患者 MT1-MMP 的表达水平。随后，构建靶向 MT1-MMP 的重组短发夹 RNA（shRNA）载体，沉默胃癌细胞中 MT1-MMP 的表达。然后，通过反转录定量聚合酶链反应（RT-qPCR）和 Western blot 分析验证抑制效率。通过细胞计数试剂盒-8 试验和 Transwell 试验检测 MT1-MMP 沉默对细胞增殖和侵袭的影响。通过 RT-qPCR 检测波形蛋白和上皮钙黏蛋白（E-钙黏蛋白）的表达水平。免疫组织化学分析结果显示，与非癌旁组织相比，胃癌组织中 MT1-MMP 的表达明显过表达。与非癌源性 GES-1 细胞相比，癌源性细胞系 AGS 细胞中 MT1-MMP 的表达水平也明显升高。此外，AGS 细胞中 MT1-MMP 的表达水平通过 shRNA 转染显著降低。AGS 细胞中 MT1-MMP 水平下调后，细胞增殖和侵袭明显受到抑制。这些抑制作用与波形蛋白表达降低和 E-钙黏蛋白表达增加有关。MT1-MMP 在胃癌细胞中过表达，沉默 MT1-MMP 通过调节波形蛋白和 E-钙黏蛋白的表达抑制细胞的增殖和侵袭。
