中文摘要：

目的：探讨RNA干扰构成型光形态建成同源亚基3（COPS3）基因对肺癌细胞A549增殖的抑制作用,初步阐明其作用机制。方法：选取肺腺癌细胞系A549建立裸小鼠成瘤实验模型,将40只小鼠随机分为实验组（移植感染si-COPS3的A549细胞）和对照组（移植感染si-CTRL的A549细胞）,每组20只,检测实验组和对照组裸小鼠体内的成瘤体积、质量和成瘤速率。应用Westernblotting检测抑制COPS3基因表达后细胞周期相关蛋白P21、CDK2、CDK4、cyclinB1和cyclinD1表达水平。结果：实验组裸小鼠体内成瘤体积和质量显著小于对照组（P〈0.05）,成瘤速率较对照组明显下降。与对照组比较,实验组小鼠细胞P21蛋白表达水平明显上调（P〈0.05）,cyclinB1和CDK4表达水平下调（P〈0.05）,而cyclinD1与CDK2表达水平无明显变化（P=0.384,P=0.605）。结论：COPS3基因表达受抑制使肺癌细胞增殖能力明显下降,其作用机制与P21表达上调、cyclinB1和CDK4表达下调有关联。

英文摘要：

Objective To investigate the inhibitory effect of constitutive photomorphogenic homolog subunit 3 of COP9（COPS3） gene interferred by RNA on the proliferation of lung cancer A549 cells, and to clarify its mechanism. Methods The tumor experimental models of nude mice were established in lung cancer cell line A549. 40 nude mice were divided into experiment group （n = 20, implanted with A549 cells infected by si-COPS3） and control group（n = 20, implanted with A549 cells infected by si-CTRL. The tumor size, weight, and tumor formation rate of the nude mice were detected. The expression levels of the cell cycle related proteins, such as P21, CDK2, CDK4, cyclinB1, and cyclinD1 were detected by Western blotting method after down-regulation of expresion of COPS3 gene in A549 cells. Results The tumor volume and weight （P 〈 0.05）, and the tumor formation rate of nude mice in experiment group were significantly lower than those in control group. Compared with control group, the expression level of P21 protein was up-regulated（P〈0.05）, and the expression levels of CDK4 and cyclinB1 protein were down-regulated （P〈 0.05）, while the expression levels of CDK2 and cyclinD1 protein had no significant changes（P〈0. 384, P=0. 605）. OonclusJon The proliferation of lung cancer cells can be suppressed significantly by inhibiting the expression of COPS3 gene. This effect may be mqdiated by up-regulating the expression of P21 and down-regulating the expressions of cyclinB1 and CDK4.