Reversing multidrug resistance by RNA interference through the suppression of MDR1 gene in human hepatoma cells

World J Gastroenterol. 2006 Jun 7;12(21):3332-7. doi: 10.3748/wjg.v12.i21.3332.

Abstract

Aim: To reverse the multidrug resistance (MDR) by RNA interference (RNAi)-mediated MDR1 suppression in hepatoma cells.

Methods: For reversing MDR by RNAi technology, two different short hairpin RNAs (shRNAs) were designed and constructed into pGenSil-1 plasmid, respectively. They were then transfected into a highly adriamycin-resistant HepG2 hepatoma cell line (HepG2/ADM). The RNAi effect on MDR was evaluated by real-time PCR, cell cytotoxicity assay and rhodamine 123 (Rh123) efflux assy.

Results: The stably-transfected clones showed various degrees of reversal of MDR phenotype. Surprisingly, the MDR phenotype was completely reversed in two transfected clones.

Conclusion: MDR can be reversed by the shRNA-mediated MDRI suppression in HepG2/ADM cells, which provides a valuable clue to make multidrug-resistant hepatoma cells sensitive to anti-cancer drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
  • Antibiotics, Antineoplastic / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics*
  • Cell Line, Tumor
  • Doxorubicin / therapeutic use
  • Drug Resistance, Multiple / genetics*
  • Drug Resistance, Multiple / physiology*
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / physiology
  • Gene Expression Regulation, Neoplastic
  • Genes, MDR / genetics*
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics*
  • Phenotype
  • RNA / pharmacology
  • RNA Interference / physiology*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Suppression, Genetic / drug effects
  • Suppression, Genetic / genetics*
  • Transfection

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA
  • Doxorubicin