Therapeutic value of orally administered silibinin in renal cell carcinoma: manipulation of insulin-like growth factor binding protein-3 levels

BJU Int. 2007 Aug;100(2):438-44. doi: 10.1111/j.1464-410X.2007.07012.x.

Abstract

Objectives: To investigate if the feeding of silibinin (an anticancer flavonoid) to mice inhibits in vivo renal cell carcinoma (RCC) growth via changes in insulin-like growth factor binding protein-3 (IGFBP-3) levels.

Materials and methods: Male severe combined immunodeficiency disease (SCID) mice (7 weeks old), with left kidneys injected with 1 million SN12K1 cells, were fed a silibinin-containing diet (0.1%, 0.2% and 0.4% w/w) or control AIN-93G diet for 39 days from 1 day after tumour engraftment.

Results: There was a reduction in tumour deposits and tumour kidney weight in SCID mice fed with a 0.4% silibinin-containing diet compared to those fed the control diet. Mice with tumour injection (silibinin or control-diet group) had constant total body weight and food consumption. The mean plasma and tumourous kidney silibinin concentrations, as measured by high-pressure liquid chromatography-tandem mass spectrometry, increased with escalating doses of silibinin. Using real-time polymerase chain reaction and enzyme-linked immunosorbent assay, the mean tissue IGFBP-3 mRNA (in SN12K1-implanted kidney) and plasma IGFBP-3 levels increased in mice fed with 0.1% silibinin (tumour IGFBP-3 mRNA levels, 156% higher vs control-diet group, P = 0.007; and plasma IGFBP-3 levels, 61% higher vs control-diet group, P = 0.002) but not in mice fed with the higher silibinin pellet strengths.

Conclusion: Oral administration of silibinin suppressed local and metastatic tumour growth in vivo in an orthotopic xenograft model of RCC. This anti-neoplastic action of silibinin might involve IGFBP-3. The exact mechanism through which IGFBP-3 promotes silibinin's anticancer effects warrants further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Analysis of Variance
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antioxidants / administration & dosage*
  • Carcinoma, Renal Cell / drug therapy*
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Kidney Neoplasms / drug therapy*
  • Male
  • Mice
  • Mice, SCID
  • Reverse Transcriptase Polymerase Chain Reaction
  • Silybin
  • Silymarin / administration & dosage

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Insulin-Like Growth Factor Binding Protein 3
  • Silymarin
  • Silybin