Inhibitory effect of silibinin on EGFR signal-induced renal cell carcinoma             progression via suppression of the EGFR/MMP-9 signaling pathway.
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.
Department of Urology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, PR China.
Liang
L
Liang
Lei
L
Li
Jin
J
Zeng
Yang
Y
Gao
Yu-Le
YL
Chen
Zhi-Qiang
ZQ
Wang
Xin-Yang
XY
Wang
Luke S
LS
Chang
Dalin
D
He
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D012838:Silymarin; D000077385:Silybin; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9