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细胞周期蛋白D1反义寡脱氧核苷酸对胃癌细胞生长及G1期调节因子表达的影响

Effects of cyclin D1 antisense oligodeoxyneucleotides on the growth and expression of G1 phase regulators in gastric carcinoma cells.

作者信息

Shuai Xiaoming, Han Gaoxiong, Wang Guobin

机构信息

Department of General Surgery, Xiehe Hospital, Tongji Medical Collage, Huazhong University of Science and Technology University, Wuhan 430022.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2003;23(4):396-8, 406. doi: 10.1007/BF02829427.

Abstract

To investigate the effects of Cyclin D1 antisense oligodeoxyneucleotides (ASODN) on the growth, cell cycle progression and expression of G1 phase regulators in human gastric carcinoma cell lines SGC7901 and HS746T, phosphorothioate-modified Cyclin D1 ASODN were encapsulated by LipofectAMINE2000 and transfected into gastric carcinoma cells. Dose-dependent inhibitory effects were induced by Cyclin D1 ASODN in two gastric carcinoma cell lines. Treatment of gastric carcinoma cells with 0.2 micromol/L Cyclin D1 ASODN for 24 h could significantly inhibit their growth in vitro and in vivo, reduce expression of Cyclin D1 mRNA to 26.3% (SGC7901) and 17.3% (HS746T) respectively. The percentage of cells in G0/G1 phase was increased as revealed by flow cytometry. Immunohistochemical staining showed that the expression of p21 was increased and the expression of Cyclin D1 and pRb was decreased in the two cell lines; the expression of p27 was increased in HS746T, but unchanged in SGC7901. Cyclin D1 ASODN could inhibit the growth and the expression of Cyclin D1 mRNA in gastric carcinoma cells, influence the cell cycle and expression of its regulators.

摘要

为研究细胞周期蛋白D1反义寡脱氧核苷酸(ASODN)对人胃癌细胞系SGC7901和HS746T生长、细胞周期进程及G1期调节因子表达的影响,用脂质体转染试剂2000包裹硫代磷酸修饰的细胞周期蛋白D1 ASODN并转染至胃癌细胞。细胞周期蛋白D1 ASODN在两种胃癌细胞系中诱导出剂量依赖性抑制作用。用0.2 μmol/L细胞周期蛋白D1 ASODN处理胃癌细胞24小时可显著抑制其体外和体内生长,使细胞周期蛋白D1 mRNA表达分别降至26.3%(SGC7901)和17.3%(HS746T)。流式细胞术显示G0/G1期细胞百分比增加。免疫组化染色表明,两细胞系中p21表达增加,细胞周期蛋白D1和pRb表达降低;HS746T中p27表达增加,而SGC7901中无变化。细胞周期蛋白D1 ASODN可抑制胃癌细胞生长及细胞周期蛋白D1 mRNA表达,影响细胞周期及其调节因子的表达。

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