Suppression of glucosylceramide synthase by RNA interference reverses multidrug resistance in human breast cancer cells

Neoplasma. 2006;53(1):1-8.


Glucosylceramide synthase (GCS), the enzyme that converts ceramide to glucosylceramide, induce multidrug resistance (MDR) in cancer cells. Recently, RNA interference (RNAi) is a powerful strategy for gene therapy by introducing double-stranded RNA and leading to the sequence-specific destruction. We have designed two different short hairpin RNAs (shRNAs) targeting GCS and introduced them into adriamycin- resistant human breast cancer cells (MCF-7/AdrR cells) to inhibit GCS expression. The results demonstrated that the shRNAs targeting GCS decreased GCS mRNA, abolished GCS protein levels and restored the sensitivity of MCF-7/AdrR cells to several antineoplastic drugs. This study revealed that this approach can reverse MDR effectively and it may be applicable to cancer patients as a specific means to restore the sensitivity to chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Blotting, Western
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology*
  • Cell Line, Tumor
  • Drug Resistance, Multiple / physiology*
  • Drug Resistance, Neoplasm / physiology*
  • Female
  • Gene Silencing
  • Genetic Therapy
  • Glucosyltransferases / metabolism*
  • Humans
  • RNA Interference*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection


  • Antineoplastic Agents
  • RNA, Messenger
  • Glucosyltransferases
  • ceramide glucosyltransferase