Luo Zhiguo, Dong Xiaoxia, Ke Qing, Duan Qiwen, Shen Li
Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Department of Pharmacology, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Oncol Lett. 2014 Jul;8(1):361-366. doi: 10.3892/ol.2014.2115. Epub 2014 May 7.
Metastasis is considered to be the major cause of mortality in patients with cancer, and gastric cancer is a highly metastatic cancer. In the present study, the anti-metastatic activity of chitooligosaccharide (COS) in human gastric cancer cells and its underlying mechanism were investigated. It was found that COS significantly inhibited SGC-7901 cell proliferation and metastasis in a dose-dependent manner, as observed by MTT, wound-healing and Transwell assays. Quantitative real-time polymerase chain reaction and western blot analysis indicated that COS could decrease the expression of cluster of differentiation 147 (CD147) and subsequently reduce matrix metalloproteinase-2 (MMP-2) expression. A clear dose-dependent inhibition of MMP-2 activity was also observed in SGC-7901 cells following treatment with COS in gelatin zymography experiments. Furthermore, overexpression of CD147 (when transfected with pEGFP-C1 plasmid) in SGC-7901 cells partially protected against COS-induced inhibition of MMP-2. The results of the present study demonstrated the potential of COS in suppressing gastric cancer metastasis, and that the CD147/MMP-2 pathway may be involved as the key mechanism of its anti-metastatic effect.
转移被认为是癌症患者死亡的主要原因,而胃癌是一种具有高度转移性的癌症。在本研究中,研究了壳寡糖(COS)在人胃癌细胞中的抗转移活性及其潜在机制。通过MTT、伤口愈合和Transwell实验观察发现,COS以剂量依赖性方式显著抑制SGC-7901细胞增殖和转移。定量实时聚合酶链反应和蛋白质印迹分析表明,COS可降低分化簇147(CD147)的表达,随后降低基质金属蛋白酶-2(MMP-2)的表达。在明胶酶谱实验中,用COS处理SGC-7901细胞后,也观察到MMP-2活性有明显的剂量依赖性抑制。此外,SGC-7901细胞中CD147的过表达(用pEGFP-C1质粒转染时)部分抵消了COS对MMP-2的抑制作用。本研究结果证明了COS在抑制胃癌转移方面的潜力,并且CD147/MMP-2途径可能作为其抗转移作用的关键机制参与其中。