Oral silibinin inhibits in vivo human bladder tumor xenograft growth involving down-regulation of survivin.

PURPOSE: Chemoprevention is an upcoming approach to control bladder cancer, which is one of the commonly diagnosed malignancies showing recurrence rate of 70% or even higher. Recently, we observed the in vitro efficacy of silibinin, a flavanolignan, in human bladder transitional cell papilloma RT4 cells. Here, we investigated the antitumor efficacy and associated mechanisms of silibinin in RT4 tumor xenograft. EXPERIMENTAL DESIGN: RT4 tumor xenograft was implanted s.c. in athymic nude mice, and then animals were oral gavaged with silibinin at 100 and 200 mg/kg doses, 5 days/week for 12 weeks. Tumor growth, body weight, and diet consumption were recorded, and tumors were analyzed for proliferation, apoptosis, and angiogenesis biomarkers and molecular alterations by immunohistochemistry, immunoblot analysis, and ELISA. p53 small interfering RNA was used in cell culture to examine the role of p53 in survivin expression. RESULTS: Silibinin feeding inhibited tumor xenograft growth without any gross signs of toxicity. Silibinin decreased tumor volume by 51% to 58% (P