Reduced high-mobility group box 1 expression induced by RNA interference inhibits the bioactivity of hepatocellular carcinoma cell line HCCLM3

Dig Dis Sci. 2012 Jan;57(1):92-8. doi: 10.1007/s10620-011-1944-z. Epub 2011 Oct 26.

Abstract

Background: Increased expression of high-mobility group box 1 (HMGB1) has been observed in many tumor types, but the role of HMGB1 in hepatocellular carcinoma (HCC) is unknown.

Aims: To examine the effects of RNA interference HMGB1 on the bioactivity of HCC cell line HCCLM3.

Methods: We synthesized three specific small interfering RNAs of HMGB1 (HMGB1-siRNAs) and transfected these into HCCLM3 cells by use of Lipofectamine 2000. RT-PCR and Western blot were performed to determine the effects of HMGB1-siRNAs on HMGB1 expression and to detect NF-κB/p65 and VEGF-C expression after transfection of HMGB1-siRNAs into HCCLM3. In vitro proliferation was assessed by MTT assay. Migration and invasive ability were determined by use of the Transwell assay. Apoptosis was demonstrated by flow cytometry.

Results: RT-PCR and Western blotting showed that all three specific HMGB1-siRNAs significantly inhibited HMGB1 expression, with inhibition by HMGB1-siRNA-1 being highest (70-80%). MTT assay demonstrated that the growth of cells transfected with HMGB1-siRNA-1 was significantly lower than that of control cells (P < 0.01). The Transwell assay showed that cell migration and invasion were significantly inhibited in HMGB1 knockdown cells compared with control cells (P < 0.01). FCM revealed that apoptosis was significantly increased in HMGB1-siRNA-1-transfected cells compared with control cells (P < 0.01). Expression of NF-κB/p65 and VEGF-C was inhibited in HCCLM3 cells transfected with HMGB1-siRNA-1 compared with control cells (P < 0.01).

Conclusion: Downregulation of HMGB1 could obviously inhibit the growth of HCCLM3 cells, and their migration and invasion ability. HMGB1 may serve as a potential target for treatment of HCC.

Publication types

  • Comparative Study

MeSH terms

  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • HMGB1 Protein / metabolism*
  • Humans
  • In Vitro Techniques
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • RNA Interference*
  • RNA, Small Interfering / pharmacology*
  • Transfection
  • Vascular Endothelial Growth Factor C / metabolism

Substances

  • HMGB1 Protein
  • NF-kappa B
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor C