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

Horng Rong Chang, Pei Ni Chen, Shun Fa Yang, Ying Sui Sun, Sheng Wen Wu, Tung Wei Hung, Jong Da Lian, Shu Chen Chu, Yih Shou Hsieh

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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 50μM, 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.

Original languageEnglish
Pages (from-to)811-823
Number of pages13
JournalMolecular Carcinogenesis
Volume50
Issue number10
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

Keywords

  • MMP
  • Renal cell carcinoma
  • Silibinin
  • TIMP-2
  • U-PA

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this