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郭长升,韩怀忠,徐琦,宋书杰,孙立东,石磊,盛之玲,赵洁.S100A11表达下调对胃癌MKN-45细胞增殖和侵袭的影响[J].陆军军医大学学报(原第三军医大学学报),2013,35(24 ):2665-2670. Guo Changsheng,Han Huaizhong,Xu Qi,Song Shujie,Sun Lidong,Shi Lei,Sheng Zhiling,Zhao Jie.Effects of S100A11 expression down-regulation on proliferation and invasion in gastric carcinoma MKN-45 cells[J].J Amry Med Univ (J Third Mil Med Univ),2013,35(24 ):2665-2670.
郭长升, 韩怀忠, 徐琦, et al. Effects of S100A11 expression down-regulation on proliferation and invasion in gastric carcinoma MKN-45 cells[J]. Journal of Army Medical University, 2013, 35(24): 2665-2670.
郭长升,韩怀忠,徐琦,宋书杰,孙立东,石磊,盛之玲,赵洁.S100A11表达下调对胃癌MKN-45细胞增殖和侵袭的影响[J].陆军军医大学学报(原第三军医大学学报),2013,35(24 ):2665-2670. Guo Changsheng,Han Huaizhong,Xu Qi,Song Shujie,Sun Lidong,Shi Lei,Sheng Zhiling,Zhao Jie.Effects of S100A11 expression down-regulation on proliferation and invasion in gastric carcinoma MKN-45 cells[J].J Amry Med Univ (J Third Mil Med Univ),2013,35(24 ):2665-2670. DOI:
郭长升, 韩怀忠, 徐琦, et al. Effects of S100A11 expression down-regulation on proliferation and invasion in gastric carcinoma MKN-45 cells[J]. Journal of Army Medical University, 2013, 35(24): 2665-2670. DOI:
目的 研究S100A11表达下调对胃癌细胞增殖、细胞周期和侵袭的影响。 方法 采用Western blot检测不同胃癌细胞株(MKN-28、SGC-7901和MKN-45)和正常胃黏膜上皮细胞(GES-1)中S100A11 蛋白的表达。将S100A11 siRNA 和对照siRNA分别转染MKN-45细胞,将细胞分为3组:未处理组、对照siRNA组和S100A11 siRNA组。采用Western blot检测转染前后S100A11蛋白的表达,并利用CCK-8试剂、流式细胞术及Boyden小室分别检测3组细胞的增殖、细胞周期和细胞侵袭能力的变化,最后采用Western blot分析细胞周期和侵袭相关蛋白的表达。 结果 S100A11蛋白在胃癌组织中表达的阳性率(69.81%,37/53)明显高于正常胃黏膜组织(16.98%,9/53) (χ
2
=30.110
P=0.000)。3株胃癌细胞株中S100A11蛋白表达水平显著高于正常胃黏膜上皮细胞(P0.05),其中S100A11在MKN-45细胞中的表达水平显著高于MKN-28和SGC-7901(P0.05)。S100A11 siRNA能显著下调MKN-45细胞中S100A11蛋白的水平,其表达下调显著抑制细胞的增殖、改变细胞周期分布和降低细胞的侵袭能力。S100A11表达下调能显著降低Cyclin D1、Cdk2和MMP-2蛋白的表达,但增加E-cadherin蛋白的表达水平。 结论 S100A11介导胃癌细胞生物学行为的变化可能与Cyclin D1、Cdk2、E-cadherin和MMP-2表达变化密切相关,因而抑制S100A11的水平可能是胃癌潜在的分子治疗靶点。
Objective To investigate the effects of S100A11 expression down-regulation on the proliferation
cell cycle and invasion in gastric carcinoma cells. Methods Expression of S100A11 protein was examined in 3 gastric carcinoma cell lines (MKN-28
SGC-7901 and MKN-45) and normal gastric mucous epithelial cell GES-1 by Western blotting. S100A11 siRNA and control siRNA were utilized to transfect MKN-45 cells
which were divided into 3 groups
untreated group
control siRNA group and S100A11 siRNA group. Expression of S100A11 protein was investigated after transfection by Western blotting. Subsequently
the changes of cell proliferation
cell cycle and cell invasion were detected by CCK-8 kit
flow cytometry and Boyden chamber assay
respectively. Finally
the expressions of cell cycle- and invasion-related proteins were analyzed by Western blotting. Results Positive expression ratio of S100A11 in gastric carcinoma tissues was significantly higher than that in normal gastric mucous epithelial tissues (Chi square=30.110
P=0.000). The levels of S100A11 protein expression in the 3 gastric carcinoma cell lines were significantly higher than that in normal gastric mucous epithelial cells (P0.05). In addition
expression of S100A11 protein in MKN-45 cells was markedly higher than that in MKN-28 and SGC-7901 cells (P0.05). S100A11 siRNA significantly downregulated the level of S100A11 protein in MKN-45 cells
and the downregulation evidently suppressed cell proliferation
altered cell cycle distribution and reduced cell invasion ability. Most notably
the downregulation of S100A11 expression significantly evoked the expression decrease of Cyclin D1
Cdk2 and MMP-2 and increase of E-cadherin. Conclusion S100A11 mediates the alterations of biological behaviors of gastric carcinoma cells
which may be tightly associated with the expression changes of Cyclin D1
Cdk2
E-cadherin and MMP-2. Thus
S100A11 may be a potential molecular therapy target of gastric carcinoma.
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