目的：探讨靶向血管内皮生长因子（vascular endothelial growth factor，VEGF）基因的siRNA对乳腺癌MCF-7细胞的抑制效果。方法：设计靶向VEGF的4种小干扰RNA（small interfering RNA，siRNA），包括对称siRNA（siRNA21/21，siRNA23/23）与不对称siRNA（asymmetric siRNA, aiRNA；aiRNA21/23，aiRNA19/21）。siRNA转染入MCF-7细胞后，MTT及流式细胞术检测MCF-7细胞增殖及凋亡情况，RT-PCR、ELISA法检测MCF-7细胞中VEGF基因和蛋白的表达。结果：与对照组相比，aiRNA21/23、siRNA23/23、aiRNA19/21、siRNA21/21这4种siRNA都能有效抑制VEGF mRNA的表达\[（71.4±501）%、（40.0±3.11）%、（37.2±2.79）%、（11.1±0.99）%vs （2.4±0.11）%，P<0.01\]，且抑制MCF-7细胞的增殖\[(44.7±538)%、（38.5±5.67）%、（33.6±2.18）%、（33.1±3.18）%vs（2.2±0.28）%，P<0.01\]，其中以不对称aiRNA21/23的抑制效果最明显。与对照组比较，aiRNA21/23显著促进MCF-7细胞的凋亡\[(49.9±4.02）% vs (4.7±0.91)%， P<0.01\]。结论：靶向VEGF基因的siRNA可抑制MCF-7细胞的增殖、促进细胞凋亡，尤以不对称siRNA的效果最明显。

Objective: To investigate the inhibitiory effect of siRNA targeting vascular endothelial growth factor (VEGF) gene on proliferation of breast cancer MCF-7 cells. Methods: Small interfering RNA (siRNA) targeting VEGF, including 2 siRNAs (siRNA21/21, siRNA23/23) and 2 asymmetric siRNAs (aiRNA) (aiRNA19/21, aiRNA21/23) were designed and synthesized. The siRNA was transfected into MCF-7 cells, and cell proliferation was detected by MTT method, and the apoptosis was analyzed by flow cytometry. VEGF protein and mRNA expression levels of MCF-7 cells were detected by ELISA and RT-PCR. Results: Compared with the control group, the 4 siRNAs effectively inhibited VEGF mRNA expression (\[714±5.01\]%, \[40.0±3.11\]%, \[37.2±2.79\]%, \[11.1±0.99\]% vs \[2.4±0.11\]%, P<005), and the proliferation of MCF-7 cells (\[44.7±5.38\]%, \[38.5±5.67\]%, \[33.6±2.18\]%, \[33.1±318\]%, \[2.2±0.28\]%, P<0.05), with aiRNA21/23 of the best RNA interference effect. Compared with the control group, the apoptotic rate was significantly increased (\[49.9±4.02\]% vs \[4.7±0.91\]%, P<0.05). Conclusion:siRNA targeting VEGF can inhibit proliferation and induce apoptosis of MCF-7 cells, with asymmetric siRNA showing best effects.

国家重大新药创制项目资助（No. 2009ZX09103-635）