Effects and mechanisms of silibinin on human hepatocellular carcinoma xenografts in nude mice

World J Gastroenterol. 2009 Apr 28;15(16):1943-50. doi: 10.3748/wjg.15.1943.


Aim: To investigate the in vivo effects and mechanisms of silibinin on the growth of hepatocellular carcinoma (HCC) xenografts in nude mice.

Methods: Nude mice bearing HuH7 xenografts were used to assess the anti-HCC effects and mechanisms of silibinin.

Results: Silibinin resulted in a potent dose-dependent reduction of HuH7 xenografts in association with a significant decrease in Ki-67 and alpha-fetoprotein production, nuclear NF-kappaB content, polo-like kinase 1, Rb phosphorylation, and E2F1/DP1 complex, but increased p27/CDK4 complex and checkpoint kinase 1 expression, suggesting that the in vivo effects of silibinin are mediated by inhibiting G1-S transition of the cell cycle. Silibinin-induced apoptosis of HuH7 xenografts was associated with inhibited survivin phosphorylation. Silibinin-reduced growth of HuH7 xenografts was associated with decreased p-ERK, increased PTEN expression and the activity of silibinin was correlated with decreased p-Akt production, indicating involvement of PTEN/PI(3)K/Akt and ERK pathways in its in vivo anti-HCC effects. Silibinin-reduced growth of HuH7 xenografts was also associated with a significant increase in AC-H3 and AC-H4 expression and the production of superoxide dismutase (SOD)-1.

Conclusion: Silibinin reduces HCC xenograft growth through the inhibition of cell proliferation, cell cycle progression and PTEN/P-Akt and ERK signaling, inducing cell apoptosis, and increasing histone acetylation and SOD-1 expression.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Dietary Supplements
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Histones / metabolism
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Mice
  • Mice, Nude
  • Microtubule-Associated Proteins / metabolism
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Repressor Proteins
  • Silybin
  • Silymarin / metabolism
  • Silymarin / pharmacology
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Survivin
  • Transplantation, Heterologous*
  • alpha-Fetoproteins / metabolism


  • Antioxidants
  • Birc5 protein, mouse
  • Histones
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Repressor Proteins
  • SOD1 protein, human
  • Silymarin
  • Survivin
  • alpha-Fetoproteins
  • Silybin
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases