SB-431542抑制乳腺癌细胞BT-549的增殖和侵袭及其机理研究  

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

作　　者：曾凡才[1,2] 何宗洋 莫冬阳 周红[1] 

机构地区：[1]电子科技大学生命科学与技术学院,成都610054 [2]泸州医学院生物化学与分子生物学实验室,泸州646000

出　　处：《中国细胞生物学学报》2014年第5期602-609,共8页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:30972280)资助的课题~~

摘　　要：肿瘤转移是导致肿瘤患者死亡的最主要原因，TGF-β超家族成员Nodal分子被证实参与肿瘤细胞的增殖和转移，因而基于Nodal信号为靶标开展抗肿瘤研究成为可能。该研究应用Western blot检测乳腺癌细胞株BT-549、T-47D、MCF-7、SK-BR-3和MDA—MB-231中的Nodal和基质金属蛋白酶-2（matrix metalloproteinase-2，MMP-2）的表达水平，发现它们在BT-549细胞中表达量最高。然后采用不同浓度_Nodal信号抑制剂SB．431542（1-50μmol／L）处理BT-549细胞48h，利用MTT法揭示20～50gmol／L的SB-431542抑制该细胞增殖。进一步利用细胞划痕和Transwell实验证明，10μmol／L的SB-431542可抑制乳腺癌细胞的迁移和侵袭。最后，通过明胶酶谱和Westernblot显示，10～30gmol／L的sB．431542可剂量依赖性地抑制MMP-2的表达和活性。上述结果说明，SB-431542通过阻断Nodal信号通路可效抑制乳腺癌细胞BT-549的增殖、迁移和侵袭，其作用机制可能与降低MMP-2的表达和活性有关。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） signifi- cantly 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 （10-30μmol/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.

关 键 词：乳腺癌 NODAL 基质金属蛋白酶-2 SB-431542 

分 类 号：R737.9[医药卫生—肿瘤]