目的：探讨肿瘤坏死因子相关凋亡诱导配体（tumor necrosis factor-related apoptosis-inducing ligand，TRAIL）抑制乳腺癌MDA-MB-231细胞侵袭能力的可能机制。方法：Western blotting、Real-time PCR分别检测rsTRAIL处理对MDA-MB-231细胞内EGFR、磷酸化转录因子IκBα（p-IκBα）和 miR-146a表达的影响。向MDA-MB-231细胞转染miR-146a mimics、miR-146a inhibitor，Western blotting检测miR-146a对MDA-MB-231细胞中EGFR表达水平的影响。Transwell实验检测rsTRAIL、miR-146a和EGFR对MDA-MB-231细胞侵袭能力的影响。结果：20 ng/ml rsTRAIL显著抑制MDA-MB-231细胞中EGFR的表达（6 h, t=4.35, P<0.05; 12 h, t=8.609, P<0.01; 24 h, t=10.84, P<0.01），提高p-IκBα（6 h, t=-4.201, P<0.05; 12 h, t=-15.805, P<0.01; 24 h, t=-35.921, P<0.01）和miR-146a的表达水平（6 h, t=-4.67, P<0.05; 12 h, t=-11.635, P<0.01; 24 h, t=-15.8, P<0.01），并且呈时间依赖性。在MDA-MB-231细胞中转染miR-146a mimics显著抑制EGFR的表达（t=6.25, P<0.01）；反之，转染miR-146a inhibitor则促进细胞内EGFR的表达（t=-3.674, P<0.05）。rsTRAIL处理（t=7.108, P<0.01）、转染miR-146a mimics或siEGFR（t=6.051, P<0.01; t=5.245, P<0.01）均导致细胞的侵袭能力显著下降。结论：rsTRAIL通过特异性增加miR-146a的表达水平靶向降低EGFR的表达从而抑制乳腺癌MDA-MB-231细胞的侵袭能力。

Objective:To investigate the potential mechanism by which tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) inhibits the invasion capability of breast cancer MDA-MB-231 cells. Methods：After treating MDA-MB-231 cells with rsTRAIL, the expression of EGFR and p-IκBα were examined by immunoblotting, and the level of miR-146 was measured by real-time quantitative PCR. Immunoblotting was also used to detect the effect of miR-146a on EGFR expression. Transwell assay was carried out to assess the effects of rsTRAIL, miR-146a and EGFR on the invasion ability of MDA-MB-231 cells. Results: In MDA-MB-231 cells treated for 6, 12, and 24 hours, rsTRAIL(20 ng/ml) significantly suppressed the expression of EGFR (6 h, t=4.35, P<0.05; 12 h, t=8.609, P<0.01; 24 h, t=1084, P<0.01), increased the level of the phosphorylated IκBα (6 h, t=-4.201, P<0.05; 12 h, t =-15.805, P<001; 24 h, t=-35.921, P<0.01), and upregulated the expression of miR-146a (6 h, t=-4.67,P<0.05; 12 h, t=-11.635, P<0.01;24 h, t=-15.8, P<0.01), and on time dependent. Compared with that in control cells, the level of EGFR (t=625, P<0.01) was significantly decreased in MDA-MB-231 cells transfected with miR-146a mimics, whereas in the same cells transfected with miR-146 inhibitor the expression of EGFR promoted (t=-3.674, P<005). Furthermore, transfection with rsTRAIL, as well as transfection with miR-146a mimics or siEGFRall dramatically decreased the invasion ability of MDA-MB-231 cells (t=7.108, P<0.01; t=6.051, P<0.01; t=5.245, P<0.01 respectively). Conclusion: rsTRAIL specifically suppresses EGFR-dependent invasion capability of human breast cancer through inducing increased expression of miR-146a.