Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi)

FEBS Lett. 2003 Jun 19;545(2-3):144-50. doi: 10.1016/s0014-5793(03)00523-4.

Abstract

For reversal of MDR1 gene-dependent multidrug resistance (MDR), two small interfering RNA (siRNA) constructs were designed to inhibit MDR1 expression by RNA interference. SiRNA duplexes were used to treat human pancreatic carcinoma (EPP85-181RDB) and gastric carcinoma (EPG85-257RDB) cells. In both cellular systems, siRNAs could specifically inhibit MDR1 expression up to 91% at the mRNA and protein levels. Resistance against daunorubicin was decreased to 89% (EPP85-181RDB) or 58% (EPG85-257RDB). The data indicate that this approach may be applicable to cancer patients as a specific means to reverse tumors with a P-glycoprotein-dependent MDR phenotype back to a drug-sensitive one.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / drug therapy
  • Carcinoma / genetics
  • Daunorubicin / pharmacology
  • Gene Expression Regulation, Neoplastic*
  • Genes, MDR / genetics*
  • Humans
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / genetics
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • RNA, Small Interfering / pharmacology*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics
  • Tumor Cells, Cultured

Substances

  • RNA, Messenger
  • RNA, Neoplasm
  • RNA, Small Interfering
  • Daunorubicin