目的： 观察siRNA沉默信号素 4D(semaphorin 4D, Sema 4D）对乳腺癌MDA-MB-231细胞增殖、迁移的影响。方法： 构建靶向Sema 4D基因的siRNA，脂质体法转染MDA-MB-231细胞系，通过实时荧光定量-PCR、Western blotting检测干扰效率，筛选有效序列。siRNA有效干扰MDA-MB-231细胞Sema 4D表达后，CCK-8法及Transwell迁移实验检测细胞增殖及迁移能力的变化。结果：Sema 4D siRNA转染MDA-MB-231细胞后Sema 4D的（mRNA及蛋白）表达水平明显下降（P<0.05），其中以siRNA-C最明显（P<0.05）；与空白、阴性对照组相比，siRNA-C沉默MDA-MB-231细胞Sema 4D表达可明显抑制MDA-MB-231细胞增殖（均P<0.05），同时明显减弱细胞的迁移能力\[穿膜细胞数：（105.60±12.07） vs（196.20±9.04）、（186.40±6.69）个，均P<0.05\]。结论： siRNA沉默Sema 4D可抑制MDA-MB-231细胞增殖，并抑制细胞迁移，可作为乳腺癌基因治疗的潜在位点。

Objective:To investigate the effects of siRNA-mediated Semaphorin 4D (Sema 4D) gene silence on the proliferation and migration of breast cancer MDA-MB-231 cells. Methods:Small inference RNA targeting different regions of Sema 4D gene were transfected into MDA-MB-231 cells by lipofectamine 2000. The most effective siRNA in knockdown Sema 4D was screened by using quantitative PCR and Western blotting. The changes of cell proliferation and migration ability after Sema 4D knockdown were examined by CCK-8 and transwell assays. Results: MDA-MB-231 cells transfected with Sema 4D siRNA had significantly decreased expression of Sema 4D, especially in these transfected with siRNA-C (P<005). Compared with the blank and scrambled siRNA transfection groups, siRNA-C transfection significantly inhibited the proliferation of MDA-MB-231 cells (P<0.05) and their migration ability （numbers of migration cell：\[19620±904\] and \[186.40±6.69\] vs \[105.60±12.07\]，P<0.05). Conclusion: Down-regulation of Sema 4D by siRNA significantly inhibits the proliferation and migration of MDA-MB-231 cells, suggesting Sema 4Dis a novel target for breast cancer therapy.

国家自然科学基金资助项目（No.81271979)