| Objective:Studies have shown that CKIP-1 may play an important regulatory role in the occurrence and development of colorectal cancer as a tumor suppressor gene.Intestinal type gastric carcinoma often occurs on the basis of intestinal metaplasia,possibly developed through the Correa’s Cascade of chronic atrophic gastritis→IM→gastric mucosal epithelium dysplasia→intestinal type gastric carcinoma,we speculated whether CKIP-1 was also involved in the occurrence and development of intestinal type gastric carcinoma.The present study determined the expression casein kinase 2 interaction protein 1（CKIP-1）in cancer tissues of human intestinal type gastric carcinoma and human differentially differentiated intestinal type gastric carcinoma cells,and its correlations with clinical pathology features of patient and prognosis;the changes in invasive and migratory abilities of human intestinal type gastric carcinoma cells MKN28 and BGC823 that overexpressed and interfered expression of CKIP-1 were determined;the expressions of transforming growth factor-β1（TGF-β1）in cancer tissues of intestinal type gastric carcinoma patients and human different differentiated intestinal type gastric carcinoma cells were determined,and their correlations with expression of CKIP-1 were analyzed;the expressions of TGF-β1 in human intestinal type gastric carcinoma cells MKN28 and BGC823 that overexpressed and interfered expression of CKIP-1 were determined to explore the possible role of CKIP-1 in the development and progression of intestinal type gastric carcinoma and its effect on the invasive and migratory abilities of intestinal type gastric carcinoma and the possible causes,and to provide some useful experimental data for research on the pathogenesis of intestinal type gastric carcinoma.Methods:Immunohistochemical staining was used to detect the expressions of CKIP-1 in para-cancerous gastric mucosal epithelial tissues,gastrointestinal tissues and cancer tissues of 56 clinical intestinal type gastric carcinoma patients with complete clinical information of pathology and prognosis,and the correlations of expression of CKIP-1with clinicopathological parameters and prognosis were analyzed.Real-time PCR and Western blotting methods were used to detect the changes of expressions of CKIP-1mRNA and protein in human differentiated intestinal type gastric carcinoma cells MKN28,SGC7901,BGC823 and AGS;The cell models of intestinal type gastric carcinoma MKN28 and BGC823 that overexpressed and interfered expression of CKIP-1 were constructed;Scratch test,Transwell invasion,and migration tests were used to detect the invasive and migratory abilities of each cell group;Immunohistochemical staining was used to detect the expressions of TGF-β1 in cancer tissues of intestinal type gastric carcinoma patients and human differentially differentiated intestinal type gastric carcinoma cells,and their correlations with CKIP-1expressions were analyzed,Western blotting was used to detect the changes of TGF-β1expressions in intestinal type gastric carcinoma cells MKN28 and BGC823 that overexpressed and interfered expression of CKIP-1.Results:（1）Compared with the para-cancerous gastric mucosal epithelial tissue,the expression of CKIP-1 in the para-cancerous gastro-intestinal tissue was increased（P<0.01）.Compared with the para-cancerous gastro-intestinal tissue,the expression of CKIP-1 in intestinal-type gastric carcinoma tissue was decreased（P<0.05）,and 22 cases had negative or low expression of CKIP-1,34 cases had high expression of CKIP-1.The correlation analysis between CKIP-1 expression and clinicopathological parameters and prognosis of patients with intestinal type gastric carcinoma showed that CKIP-1 expression was correlated with cancer cell differentiation and TNM staging（P<0.05,P<0.01）,but was not correlated with patient age,sex,depth of tumor infiltration,and lymph node metastasis（P>0.05）,the higher the cell differentiation,the earlier the clinical staging,and the higher the expression of CKIP-1.The disease-free survival time and total survival time of the group with high expression of CKIP-1 were higher than those of the group with negative and low expression of CKIP（P<0.05）.Compared with the highly differentiated intestinal type gastric carcinoma cells MKN28,the expressions of CKIP-1 mRNA and protein in the differentiated intestinal type gastric carcinoma cells SGC7901 and the poorly differentiated intestinal type gastric carcinoma cells BGC823 and AGS were decreased（P<0.05,P<0.01）;Compared with the moderately-differentiated intestinal type gastric carcinoma cells SGC7901,the expressions of CKIP-1 mRNA and protein in poorly differentiated intestinal type gastric carcinoma cells BGC823 and AGS were decreased（P<0.01）.（2）The scratch test and Transwell migration experiment showed that,compared with the blank control group,the migration area and transmembrane cell number of intestinal type gastric carcinoma cells MKN28 and BGC823 that overexpressed CKIP-1 were decreased（P<0.05,P<0.01）,and the migration area and transmembrane cell number of intestinal type gastric carcinoma cells MKN28 and BGC823 that interfered expression of CKIP-1were increased（P<0.01）.Transwell invasion assay showed that transmembrane cell number of the intestinal type gastric carcinoma cells MKN28 and BGC823 that overexpressed CKIP-1 was decreased in comparison with the blank control group（P<0.05,P<0.01）,the number of transmembrane cells in intestinal type gastric carcinoma cells MKN28 and BGC823 that interfered the expression of CKIP-1 was increased（P<0.01）;（3）In the cancer tissues of the group of intestinal type gastric carcinoma patients,TGF-β1 was highly expressed in 24 cases and TGF-β1 was poorly expressed in 32 cases,TGF-β1 expression was negatively correlated with CKIP-1expression in cancer tissues of this group of intestinal type gastric carcinoma patients（P<0.05）.Compared with the highly differentiated intestinal type gastric carcinoma cells MKN28,the expression of TGF-β1 protein in the moderately-differentiated intestinal type gastric carcinoma cells SGC7901 was increased,but there was no significant difference between the two groups（P>0.05）,and the expressions of TGF-β1protein in the poorly differentiated intestinal type gastric carcinoma cells BGC823 and AGS were increased（P<0.01）.Compared with moderately-differentiated intestinal type gastric carcinoma cells SGC7901,the expressions of TGF-β1 protein in poorly differentiated intestinal type gastric carcinoma cells BGC823 and AGS were increased（P<0.01）;the expressions of CKIP-1 and TGF-β1 in human differentially differentiated intestinal type gastric carcinoma cells were negatively correlated（P<0.01）.Compared with the blank control group,the expressions of TGF-β1 protein in the intestinal type gastric carcinoma cells MKN28 and BGC823 that overexpressed CKIP-1 were decreased（P<0.01）,and the expressions of TGF-β1 protein in the intestinal type gastric carcinoma cells MKN28 and BGC823 that interfered expression of CKIP-1 were increased（P<0.01）.Conclusions:（1）CKIP-1 may be involved in the occurrence and development of intestinal type gastric carcinoma from gastric-intestinal tissue as a cancer suppressor gene.The expressions of CKIP-1 in the gastric carcinoma tissue and cells were correlated with the differentiation,TNM staging and prognosis of cancer cells,suggesting that the expression of CKIP-1 was related with the malignant biological behavior of intestinal type gastric carcinoma.（2）CKIP-1 expression could affect the invasive and migratory abilities of intestinal type gastric carcinoma cells,high expression of CKIP-1 could inhibit invasive and migratory abilities of intestinal type gastric carcinoma cells;（3）The CKIP-1 expressions were negatively correlated with TGF-β1 expressions in intestinal type gastric carcinoma tissue and cells,CKIP-1could negatively regulate the expression of TGF-β1 in intestinal type gastric carcinoma cells,it may be one of the reasons that CKIP-1 affected invasive and migratory abilities of intestinal type gastric carcinoma cells,but the exact molecular pathway needs further study. |
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