Nuclear factor-kappa B as a promising target for selenium chemoprevention in rat hepatocarcinogenesis

J Gastroenterol Hepatol. 2010 Apr;25(4):786-91. doi: 10.1111/j.1440-1746.2009.06160.x.

Abstract

Background and aims: Selenium's molecular mechanism for cancer chemoprevention remains unknown. We aimed to study the gene expression of nuclear factor-kappaB (NF-kappaB), tumor growth factor-alpha (TGF-alpha) and cyclin D1 and the effects of sodium selenite using preventive and therapeutic approaches in chemically-induced hepatocarcinogenesis in rats.

Methods: Rats were divided randomly into six groups: negative control, positive control (diethyl nitrosamine [DEN] + 2-acetylaminofluorene [2-AAF]), preventive group, preventive control (respective control for preventive group), therapeutic group and therapeutic control (respective control for therapeutic group). The relative gene expression of NF-kappaB, TGF-alpha and cyclin D1 in liver tissues were measured using real-time polymerase chain reaction.

Results: The findings showed that the gene expression of NF-kappaB in the preventive group and its respective control was significantly lower (P < 0.05) when compared with both the negative and positive controls. However, the expression of NF-kappaB in the positive controls and therapeutic group was significantly higher (P < 0.05) when compared with the negative controls. The expression of TGF-alpha and cyclin D1 was insignificant in all groups.

Conclusion: The inhibition of the NF-kappaB pathway in the initiation phase of hepatocarcinogenesis could be a promising target for selenium chemoprevention. However, further studies are required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Acetylaminofluorene
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Cell Transformation, Neoplastic / chemically induced
  • Cell Transformation, Neoplastic / drug effects*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Cyclin D1 / genetics
  • Diethylnitrosamine
  • Gene Expression Regulation, Neoplastic / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / genetics
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / prevention & control*
  • Male
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Selenite / pharmacology*
  • Time Factors
  • Transforming Growth Factor alpha / genetics

Substances

  • Anticarcinogenic Agents
  • Ccnd1 protein, rat
  • NF-kappa B
  • RNA, Messenger
  • Transforming Growth Factor alpha
  • Cyclin D1
  • Diethylnitrosamine
  • 2-Acetylaminofluorene
  • Sodium Selenite