Silibinin Inhibits the Invasion and Migration of Renal Carcinoma 786-O Cells In Vitro, Inhibits the Growth of Xenografts In Vivo and Enhances Chemosensitivity to 5-Fluorouracil and Paclitaxel

Silibinin is a flavonoid antioxidant that is widely used for its anti-hepatotoxic properties. It exerts a dose-dependent inhibition on the invasion and migration of 786-O renal cell carcinoma (RCC) cells in the absence of cytotoxicity. 7860 cells were treated with silibinin at various concentrations, up to 50 mu M, for a defined period and then subjected to gelatin zymography, casein zymography, and Western blot to investigate the impacts of silibinin on metalloproteinase (MMP) -2, -9, urokinase plasminogen activator (u-PA), and MAPK pathway signaling proteins, respectively. The results showed that silibinin decreased MMP-2, MMP-9, u-PA, p-p38, and p-Erk1/2 expressions in a concentration-dependent manner. The reduced expressions of MMP-2 and u-PA, as well as inhibition of cell invasion were obtained in the cultures pre-treated with PD98059 (Erk1/2 inhibitor) and SB203580 (p38 inhibitor). An in vivo anti-tumor study with a nude mice xenograft model by a subcutaneous inoculation of 786-O cells demonstrated small solid tumors after eight days following cell inoculation. There was a 70.1% reduction in tumor volume and 69.7% reduction in tumor weight by silibinin feeding on day 44, compared to those of controls. Moreover, combination treatment with silibinin and 5-fluorouracil, paclitaxel, vinblastine, or RAD-001 enhanced the chemosensitivity of 5-fluorouracil and paclitaxel. In conclusion, silibinin inhibits the invasion and migration of 786-O cells in vitro, inhibits the growth of xenografts in vivo, and enhances chemosensitivity to 5-fluorouracil and paclitaxel. (C) 2011 Wiley-Liss, Inc.