目的:研究沉默乳腺癌相关抗原1（breast cancerassociated antigen 1,BRCAA1)基因对胃癌细胞株MGC803的抑制作用及其可能的机制。方法：构建BRCAA1基因shRNA载体，将构建的shRNABRCAA1质粒与阴性对照质粒shRNAN转染胃癌MGC803细胞，24 h后用荧光显微镜观察转染效率，实时定量PCR检测 BRCAA1和GAPDH基因mRNA表达水平。MTT法检测转染后24、48与72 h的细胞增殖水平，AnnxinV PE/7AAD检测转染24 h后的细胞凋亡水平，Western blotting检测转染48 h后细胞的凋亡相关蛋白表达水平。结果：BRCAA1 siRNA表达质粒转染MGC803细胞24 h 的转染效率为（81.2±2.6）％ 。转染后48 h MGC803细胞的BRCAA1 mRNA水平下降了61.4％，MGC803细胞增殖的抑制率达45.0%，转染siRNA细胞的凋亡率明显高于未转染细胞和对照质粒转染细胞\[（14.4±１.6）% vs（5.4±2.0）％，（4.4±2.5）％，P<0.05\]。转染siRNA细胞的凋亡相关蛋白Rb与Bax的表达量显著增加（P<0.05），Bcl2的表达量显著减少（P<0.05）。结论：BRCAA1基因的沉默可有效抑制人胃癌MGC803细胞的增殖和诱导细胞凋亡，其机制与其促进Rb和Bax蛋白表达、抑制Bcl2蛋白表达有关。

Objective:To investigate the inhibitory effect of breast cancerassociated antigen 1(BRCAA1) gene silencing on gastric cancer MGC803 cells and the related mechanism. Methods: Plasmid shRNABRCAA1 and shRNAN were constructed and transfected with FuGene HD into gastric cancer cell line MGC803. The transfection efficiency was examined using fluorescent microscope 24 h later. The total RNAs was extracted 48 h after transfection and the expression of BRCAA1 and GAPDH gene were analyzed by realtime PCR. The cell proliferation was assessed by MTT assay 24 h, 48 h, and 72 h after transfection. The cell apoptosis was determined by Annexin VPE/7AAD. The expression of Rb, Bax, Bcl2 and BRCAA1 proteins was analyzed by Western blotting 48 h after transfection. Results:We found that the transfection efficiency of shRNABRCAA1 was （81.2±2.6）％ 24 h after transfection. Fortyeight hours after transfection with shRNABRCAA1 the expression of BRCAA1 mRNA decreased by 61.4%; the inhibition rate of MGC803 cells growth was 45.0%. The cell apoptosis rate of shRNABRCAA1 transfection group was significantly higher than those of untransfected group and mock plasmid transfected group （\[14.4±1.6\]% vs \[5.4±2.0\]％，\[4.4±2.5\]％，P<0.05\]. Cells transfected with shRNABRCAA1 had significantly increased expression of Rb and Bax proteins（P<0.05）, and decreased expression of Bcl2 protein（P<005）. Conclusion: BRCAA1 gene silencing can effectively inhibit the proliferation of MGC803 cells and induce apoptosis, which might be related to the promotion of Rb and Bax proteins, and suppression of Bcl2 protein.

国家重点基础研究发展（973）计划资助项目（No.2005CB723400G）； 国家高技术研究发展 （863）计划重点项目（No. 2007AA022004）；国家自然科学基金资助项目（No. 30771075；No. 30672147）； 上海市科委基金资助项目（No.072112006－6）。