title: 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.
abstract: 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. 786-O cells were treated with silibinin at various concentrations, up to 50 µM, 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. © 2011 Wiley-Liss, Inc.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Horng-Rong
authors.initials: HR
authors.lastname: Chang
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Ying-Sui
authors.initials: YS
authors.lastname: Sun
authors.forename: Sheng-Wen
authors.initials: SW
authors.lastname: Wu
authors.forename: Tung-Wei
authors.initials: TW
authors.lastname: Hung
authors.forename: Jong-Da
authors.initials: JD
authors.lastname: Lian
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000494:pharmacology; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D012838:Silymarin; D000077385:Silybin; D020928:Mitogen-Activated Protein Kinases; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D017239:Paclitaxel; D005472:Fluorouracil