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Archive > Volume 22 Issue 6 > 2015,22(6):724-628. DOI:10.3872/j.issn.1007-385X.2015.06.008 Prev Next
Basic Research
TRAIL suppresses the invasion capability of human breast cancer MDA-MB-231 cells through reducing EGFR expression
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Abstract:
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=1084, P<0.01), increased the level of the phosphorylated IκBα (6 h, t=-4.201, P<0.05; 12 h, t =-15.805, P<001; 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=625, 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<005). 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.
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