Guo Jing, Fan Kai-Xi, Xie L I, Xiao Jia-Jia, Chen Kai, Hui Li-Na, Xu Zhong-Fa
Department of Oncology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong 250031, P.R. China.
Basic Laboratory, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China.
Oncol Lett. 2015 Oct;10(4):2035-2042. doi: 10.3892/ol.2015.3604. Epub 2015 Aug 12.
The present study aimed to explore the effect and mechanism of the Kangai 1 (KAI1) gene in regulating the migration and invasion of gastric carcinoma cells, and the prognostic significance of this gene in gastric cancer patients. Immunohistochemistry and hybridization were used to investigate the role of KAI1 in the progression and prognosis of gastric cancer. The pEGFP-N1-KAI1 plasmid was transfected into human gastric carcinoma SGC7901 cells using liposomes. The effect of transfection with the KAI1 gene was measured using a reverse transcription-semi-quantitative polymerase chain reaction (RT-sqPCR) assay. The Transwell chamber assay was used to study the metastatic and invasive ability of SGC7901 cells. Gastric cancer metastasis-associated genes, including hypoxia-inducible factor (HIF)-1α, matrix metalloproteinase (MMP)-2, MMP-9, basic fibroblast growth factor (bFGF), and urease plasminogen activator (uPA) were measured by RT-sqPCR prior to and following transfection with the KAI1 gene. The expression of KAI1 protein and mRNA was associated with the differentiation degree of gastric cancer, presence of lymph node metastasis, tumor-node-metastasis stage, depth of invasion and the survival time of patients. The migratory and invasive abilities of SGC7901 cells were significantly decreased subsequent to transfection with the KAI1 gene, and the expression of bFGF and uPA was downregulated. It was concluded that the tumor suppressor gene KAI1 inhibits the migration and invasion of gastric carcinoma cells, possibly by suppressing the expression of uPA. Patients that expressed KAI1 may demonstrate an improved prognosis.
本研究旨在探讨康爱1（KAI1）基因在调控胃癌细胞迁移和侵袭中的作用及机制，以及该基因在胃癌患者中的预后意义。采用免疫组织化学和杂交技术研究KAI1在胃癌进展和预后中的作用。利用脂质体将pEGFP-N1-KAI1质粒转染至人胃癌SGC7901细胞。采用逆转录-半定量聚合酶链反应（RT-sqPCR）检测KAI1基因转染效果。运用Transwell小室实验研究SGC7901细胞的转移和侵袭能力。在转染KAI1基因前后，通过RT-sqPCR检测胃癌转移相关基因，包括缺氧诱导因子（HIF）-1α、基质金属蛋白酶（MMP）-2、MMP-9、碱性成纤维细胞生长因子（bFGF）和尿激酶型纤溶酶原激活剂（uPA）。KAI1蛋白和mRNA的表达与胃癌的分化程度、淋巴结转移情况、肿瘤-淋巴结-转移分期、浸润深度及患者生存时间相关。转染KAI1基因后，SGC7901细胞的迁移和侵袭能力显著降低，bFGF和uPA的表达下调。结论是，抑癌基因KAI1可能通过抑制uPA的表达来抑制胃癌细胞的迁移和侵袭。表达KAI1的患者可能预后较好。
