Livin gene plays a role in drug resistance of colon cancer cells

Clin Biochem. 2010 May;43(7-8):655-60. doi: 10.1016/j.clinbiochem.2010.02.004. Epub 2010 Feb 18.

Abstract

Objective: The objective of this study was to investigate the effect of knockdown of Livin expression on reversing drug resistance phenotype of colon cancer HCT-8/V cells.

Design and methods: Specific short hairpin RNA (shRNA) was chosen and transfected in human colon cancer HCT-8/V cell line. Cell apoptosis and chemosensitivity were evaluated following downregulation of Livin expression.

Results: In the current study, Livin was found to be highly expressed in the HCT-8/V colon cancer cells, which were resistant to several anti-tumor drugs. Knocking down of Livin expression in HCT-8/V cells by specific RNAi facilitated the apoptosis of HCT-8/V cells in response to vincristine (VCR), etoposide (VP-16), and 5-flourouracil (5-FU). Chemosensitivity assay confirmed the results and demonstrated the reversal of drug resistance phenotype of HCT-8/V cells.

Conclusion: These data suggest that specific silencing of Livin gene expression could be a promising target for further research in clinical chemotherapy of colon cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Blotting, Western
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Drug Resistance, Neoplasm / genetics*
  • Etoposide / pharmacology
  • Etoposide / therapeutic use
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • RNA Interference / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vincristine / pharmacology
  • Vincristine / therapeutic use

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • BIRC7 protein, human
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins
  • Vincristine
  • Etoposide
  • Fluorouracil