肠型胃癌细胞中酪蛋白激酶2相互作用蛋白1与转化生长因子β_1表达的相关性
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摘要
目的探讨酪蛋白激酶2相互作用蛋白1(CKIP-1)与转化生长因子β1(TGF-β1)在肠型胃癌细胞中表达的相关性。方法 Western blotting方法检测不同分化肠型胃癌细胞(高分化MKN28细胞、中分化SGC7901细胞和低分化BGC823、MKN45及AGS细胞)中CKIP-1与TGF-β1表达,Spearman相关性分析CKIP-1与TGF-β1表达相关性;分别构建过表达及干扰表达CKIP-1的人肠型腺癌MKN28细胞模型,Westernblotting方法检测各组细胞TGF-β1表达。结果与高分化胃癌MKN28细胞相比,中分化SGC7901细胞与低分化BGC823、MKN45及AGS细胞CKIP-1表达均降低、TGF-β1表达均升高(P <0.01);与中分化SGC7901细胞相比,低分化BGC823、MKN45及AGS细胞CKIP-1表达降低、TGF-β1表达升高(P <0.01);Spearman相关性分析显示不同分化肠型胃癌细胞中CKIP-1与TGF-β1表达负相关(r=-0.689 2,P <0.01)。与空白对照组相比,CKIP-1过表达组MKN28细胞TGF-β1表达下降(P <0.01),CKIP-1干扰表达组MKN28细胞TGF-β1表达增加(P <0.01)。结论肠型胃癌细胞中CKIP-1与TGF-β1蛋白表达负相关,CKIP-1蛋白可能通过负性上调TGF-β1表达后促进了肠型胃癌的恶性转化、发展及浸润转移。
Objective To investigate the correlation between the expression of casein kinase 2 interaction protein 1(CKIP-1)and transforming growth factorintestinal gastric cancer cells.Methods The expressions of CKIP-1 anddifferent differentiation intestinal gastric cancer cells(highly differentiated MKN28 cells,moderately differentiated SGC7901 cells,poorly differentiated BGC823 cells,MKN45 cells and AGS cells)were detected by Western blotting.The correlation between the expression of CKIP-1 andanalyzed by Spearman rank correlation analysis.The MKN28 cells with over-expressed CKIP-1 and CKIP-1 shRNA were established,respectively,and Western blotting was used to detect the expression of TGF-β1in each group.Results Compared with those in highly differentiated MKN28 cells,the expressions of CKIP-1 in moderately differentiated SGC7901 cells,poorly differentiated BGC823 cells,MKN45 cells and AGS cells were decreased whilewere increased(P<0.01).Compared with those in moderately differentiated SGC7901 cells,the expressions of CKIP-1 in poorly differentiated BGC823 cells,MKN45 cells and AGS cells were decreased butwere increased(P<0.01).Spearman rank correlation analysis showed that the expression of CKIP-1 was negatively correlated with the expression ofdifferent differentiation intestinal gastric cancer cells(r=-0.689 2,P<0.01).Compared with that in the blank control group,the expression ofdecreased in the over-expression CKIP-1 group and its expression was increased in the CKIP-1 shRNA group in MKN28 cells(P<0.01).ConclusionsThe expression of CKIP-1 is negatively correlated to the expression ofintestinal gastric cancer cells.CKIP-1 may promote the malignant transformation,development and metastasis of intestinal gastric cancer by down-regulating the expression of TGF-β_1.
Objective To investigate the correlation between the expression of casein kinase 2 interaction protein 1(CKIP-1)and transforming growth factorintestinal gastric cancer cells.Methods The expressions of CKIP-1 anddifferent differentiation intestinal gastric cancer cells(highly differentiated MKN28 cells,moderately differentiated SGC7901 cells,poorly differentiated BGC823 cells,MKN45 cells and AGS cells)were detected by Western blotting.The correlation between the expression of CKIP-1 andanalyzed by Spearman rank correlation analysis.The MKN28 cells with over-expressed CKIP-1 and CKIP-1 shRNA were established,respectively,and Western blotting was used to detect the expression of TGF-β1in each group.Results Compared with those in highly differentiated MKN28 cells,the expressions of CKIP-1 in moderately differentiated SGC7901 cells,poorly differentiated BGC823 cells,MKN45 cells and AGS cells were decreased whilewere increased(P<0.01).Compared with those in moderately differentiated SGC7901 cells,the expressions of CKIP-1 in poorly differentiated BGC823 cells,MKN45 cells and AGS cells were decreased butwere increased(P<0.01).Spearman rank correlation analysis showed that the expression of CKIP-1 was negatively correlated with the expression ofdifferent differentiation intestinal gastric cancer cells(r=-0.689 2,P<0.01).Compared with that in the blank control group,the expression ofdecreased in the over-expression CKIP-1 group and its expression was increased in the CKIP-1 shRNA group in MKN28 cells(P<0.01).ConclusionsThe expression of CKIP-1 is negatively correlated to the expression ofintestinal gastric cancer cells.CKIP-1 may promote the malignant transformation,development and metastasis of intestinal gastric cancer by down-regulating the expression of TGF-β_1.
引文
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[14]KAJDANIUK D,MAREK B,BORGIEL-MAREK H,et al.Transforming growth factor beta l(TGF beta l)in physiology and pathology[J].Endokrynol Pol,2013,64(5):384-396.
[15]李春辉,潘理会,刘海旺,等.胃癌组织中SOX2与TGF-β1、Smad3的表达及相互关系[J].实用医学杂志,2015,31(5):750-753.
[2]WANG L X,CHU M L,YIN D,et al.CKIP-1 serves as a negative regulator and correlateswith the degree of differentiation in gastric cancer[J].Int J Clin Exp Pathol,2017,10(10):10674-10680.
[3]潘理会,刘海旺,李春辉.TGF-β1、TβR-I和Smad4在胃癌发生发展中的相互关系[J].实用医学杂志,2015,31(19):3192-3194.
[4]SHEN J,ZHAO D S,LI M Z.TGF-β1 promotes human gastric carcinoma SGC7901 cells invasion by inducing autophagy[J].Eur Rev Med Pharmacol Sci,2017,21(5):1013-1019.
[5]GUO B S,ZHANG G,TANG T,et al.Increased CKIP-1 expression vs decreased TGF-beta receptor 1 expression during aginginduced cartilage degeneration in female rats[J].Bone,2010,47(Suppl 3):S419.
[6]CORREA P,PIAZUELO M B.The gastric precancerous cascade[J].J Dig Dis,2012,13(1):2-9.
[7]GONG W Y,CHEN Z Q,ZOU Y Z,et al.CKIP-1 affects the polyubiquitination of Nrf2 and Keap1 via mediating Smurf1 to resist HG-induced renal fibrosis in GMCs and diabetic mice kidneys[J].Free Radical Bio Med,2018,10(8):115,338-350.
[8]ZHAN Y T,XIE P,LI D N,et al.Deficiency of CKIP-1 aggravates high-fat diet-induced fatty liver in mice[J].Exp Cell Res,2017,355(1):40-46.
[9]PENG X,WU X,ZHANG J,et al.The role of CKIP-1 in osteoporosis development and treatment[J].Bone Joint Res,2018,7(2):173-178.
[10]胡炯,王博,吴鹏,等.CKIP-1与骨质疏松的最新研究进展[J].中国骨质疏松杂志,2016,22(8):1053-1057.
[11]CHEN G M,DING R F,TAN Y D,et al.Role of the CKIP-1gene in proliferation and apoptosis of the human lung cancer cell line H1299[J].Genet Mol Res,2015,14(2):4005-4014.
[12]常志刚,韦军民,黄美雄,等.CKIP-1、P-Akt在大肠癌组织中的表达及意义[J].医学研究杂志,2013,42(2):63-67.
[13]NIE J,LIU L,XING G,et al.CKIP-1 acts as a colonic tumor suppressor by repressing oncogenic Smurf1 synthesis and promoting Smurf1autodegradation[J].Oncogene,2014,33(28):3677-3687.
[14]KAJDANIUK D,MAREK B,BORGIEL-MAREK H,et al.Transforming growth factor beta l(TGF beta l)in physiology and pathology[J].Endokrynol Pol,2013,64(5):384-396.
[15]李春辉,潘理会,刘海旺,等.胃癌组织中SOX2与TGF-β1、Smad3的表达及相互关系[J].实用医学杂志,2015,31(5):750-753.