Inhibitory effect of silibinin on EGFR signal-induced renal cell carcinoma progression via suppression of the EGFR/MMP-9 signaling pathway
Inhibitory effect of silibinin on EGFR signal-induced renal cell carcinoma progression via suppression of the EGFR/MMP-9 signaling pathway
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水飞蓟宾通过抑制 EGFR/MMP-9 信号通路对 EGFR 信号诱导的肾细胞癌进展具有抑制作用
DOI：
10.3892/or.2012.1874
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发表时间：
2012-09-01
期刊：
影响因子：
4.2
通讯作者：
He, Dalin
中科院分区：
文献类型：
--
作者：
Liang, Liang;Li, Lei;He, Dalin
表皮生长因子（epidermal growth factor，EGF）通过其受体EGFR激活是介导肾癌转移的主要机制之一。水飞蓟宾是一种天然黄酮类抗氧化剂，具有多效抗癌能力，在多种癌症中显示出抗转移作用。然而，水飞蓟宾抑制EGFR信号诱导的RCC细胞迁移和侵袭的机制尚不清楚。在此，我们评估了影响RCC进展的EGFR信号级联的潜在作用，并研究了水飞蓟宾对EGFR信号诱导的RCC细胞迁移和侵袭能力的抑制作用。结果表明，水飞蓟宾通过阻断EGFR信号通路抑制肾癌细胞的迁移和侵袭，并呈剂量依赖性，尤其是对EGFR高表达的肾癌细胞。水飞蓟宾抑制EGFR及其下游分子ERK 1/2的磷酸化，但不影响其他下游分子STAT 3和Akt的磷酸化。此外，我们的数据表明，水飞蓟宾显着降低MMP-9的表达和活性，促进了EGFR信号，并抑制MMP-9依赖的迁移和侵袭能力的RCC细胞。综上所述，本研究清楚地表明，水飞蓟宾通过阻断EGFR/MMP-9信号传导抑制EGFR诱导的RCC细胞迁移和侵袭。因此，我们认为，水飞蓟宾可以作为一个潜在的有效的药物抑制肾癌转移。
The activation of epidermal growth factor (EGF) through its receptor, EGFR, is one of the major mechanisms that mediate renal cell carcinoma (RCC) metastasis. Silibinin, a natural flavonoid antioxidant with pleiotropic anticancer capability, has shown anti-metastatic effects in a variety of cancers. However, the mechanism by which silibinin inhibits EGFR signal-induced migration and invasion of RCC cells is not clear. Here, we evaluated the potential roles of EGFR signaling cascade that affects RCC progression, and also investigated the inhibitory effect of silibinin on the EGFR signal-induced migration and invasion abilities of RCC cells. Our data indicated that silibinin inhibited migration and invasion of RCC cells in a dose-dependent manner via blocking the EGFR signal, especially in the EGFR highly expressing RCC cells. Silibinin inhibited phosphorylation of EGFR and its downstream molecules ERK1/2 but did not affect phosphorylation of other downstream molecules, STAT3 and Akt, in human RCC cell lines. Moreover, our data suggested that silibinin significantly reduced the MMP-9 expression and its activity that was promoted by the EGFR signal, and also suppressed MMP9-dependent migration and invasion abilities of RCC cells. Taken together, this study clearly demonstrated that silibinin inhibited EGFR induced migration and invasion of RCC cells via blockade of EGFR/MMP-9 signaling. Thus, we suggest that silibinin could be used as a potential effective drug for the inhibition of RCC metastasis.