SB-431542 Inhibits the Proliferation and Invasion of Breast Cancer Cell BT-549 and Its Regulatory Mechanisms

Abstract: Metastasis is the main cause of death in patients with malignancy. Nodal， as a member of TGF-β superfamily， promotes the proliferation and metastasis of tumor cells. In this study， we hypothesized that SB-431542 as a membrane receptor-specific inhibitor of Nodal may affect the tumor properties of breast cancer cell through blocking Nodal signaling pathway. The expressions of Nodal and matrix metalloproteinase-2 (MMP-2) were detected by Western blot in breast cancer cell line BT-549， T-47D， MCF-7， SK-BR-3 and MDA-MB-231， showing that the expressions of Nodal and MMP-2 were stronger in BT549 than that in other cell lines. After the BT549 cells were treated with increasing concentrations (1~50 μmol/L) of SB-431542 for 48 h， SB-431542 (20~50 μmol/L) significantly inhibited cell proliferation but 10 μmol/L of the inhibitor had no effects. Furthermore， wound healing and Transwell assays demonstrated that 10 μmol/L of SB-431542 could block breast cancer cell migration and invasion， respectively. By gelatin zymography and Western blot， it was revealed that the expression and activity of MMP-2 but not MMP-9 were significantly suppressed by this inhibitor in a dose-dependent manner when BT-549 cells were treated by SB-431542 (10~30 μmol/L) for 48 h. Taken together， these results indicated that SB-431542 inhibited the migration and invasion of breast cancer cells through blocking Nodal signaling pathway， which might be related to the down-regulation of MMP-2 expression and activity.

CSTR: 32200.14.cjcb.2014.05.0007