Rab23 is a potential biological target for treating hepatocellular carcinoma

World J Gastroenterol. 2007 Feb 21;13(7):1010-7. doi: 10.3748/wjg.v13.i7.1010.

Abstract

Aim: To elucidate the role of Rab23 in hepatocellular carcinoma (HCC) by assessing the expression of Rab23 in HCC tissue and in HCC cell lines.

Methods: Primary tumors (n = 100) were stained with Rab23 antibodies using immunohistochemistry and in situ hybridization in tissue microarrays. Relationships between gene expression and pathology parameters were analysed. The biological significance of Rab23 in Hep-3B cells was examined by knocking down Rab23 gene expression. We designed a pair of double-stranded RNAs against human rab23 and transfected siRNA into Hep-3B cells. Rab23 expression in these cells was examined using RT-PCR and Western blots. We investigated cell growth by MTT assays and fluorescence-activated cell sorting.

Results: High cytoplasmic and nuclear expression of Rab23 was found in 38 of 71 (53.5%) and in 49 of 68 HCC patients (72%) respectively, which correlated with tumor size. HCC cell lines expressed Rab23. In Hep3B cells, siRNA for Rab23 decreased Rab23 mRNA by 4.5-fold and protein expression by 2-fold. Survival rates at 24 and 48 h for Hep-3B cells transfected with siRNA were lower and about 30% Hep-3B cells were apoptotic. Knocking down rab23 suppressed Hep3B cell growth, suggesting that rab23 could play an important role in Hep3B cell growth.

Conclusion: Rab23 is overexpressed and/or activated in HCC. Rab23 may be both a HCC predictor and a target for treating HCC.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / physiopathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hedgehog Proteins / physiology
  • Humans
  • Liver / cytology
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / physiopathology
  • RNA, Small Interfering / pharmacology
  • Signal Transduction / physiology
  • Transfection
  • rab GTP-Binding Proteins / drug effects*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / physiology*

Substances

  • Antineoplastic Agents
  • Hedgehog Proteins
  • RNA, Small Interfering
  • SHH protein, human
  • RAB23 protein, human
  • rab GTP-Binding Proteins