Silencing of 14-3-3ζ over-expression in hepatocellular carcinoma inhibits tumor growth and enhances chemosensitivity to cis-diammined dichloridoplatium

Cancer Lett. 2011 Apr 28;303(2):99-107. doi: 10.1016/j.canlet.2011.01.015. Epub 2011 Feb 22.

Abstract

The 14-3-3ζ protein plays a key role in regulation of cellular processes. In the present study, we showed that 14-3-3ζ protein was significantly overexpressed in hepatoma cell lines and human tumorous tissues of hepatocellular carcinoma (HCC) patients. Knockdown with RNA interference in hepatoma cell lines with high 14-3-3ζ expression suppressed tumor cell proliferation via activation of c-Jun N-terminal kinase (JNK) and p38/MAPK. Furthermore, suppression of 14-3-3ζ enhanced the anti-cancer effect of cis-diammined dichloridoplatium (CDDP) in hepatoma cell lines. These results suggest that silencing of 14-3-3ζ may be an attractive target for HCC therapeutic development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / genetics*
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Flow Cytometry
  • Gene Silencing*
  • Genetic Therapy / methods
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • MAP Kinase Kinase 4 / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 14-3-3 Proteins
  • Antineoplastic Agents
  • RNA, Small Interfering
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Cisplatin