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MDR1 (multidrug resistence 1) can regulate GCS (glucosylceramide synthase) in breast cancer cells

Xiaofang Zhang1, Xiaojuan Wu, Juan Li

  • 1Department of Pathology, Shandong University School of Medicine, Jinan, Shandong, PR China.

Journal of Surgical Oncology
|May 4, 2011
PubMed
Abstract

Insights

Multidrug resistance 1 (MDR1) up-regulation increases glucosylceramide synthase (GCS) expression, enhancing apoptosis in breast cancer. This study clarifies the MDR1 impact on GCS, revealing a novel therapeutic target.

Area of Science:

  • Biochemistry
  • Cancer Biology
  • Molecular Oncology

Background:

  • Multidrug resistance (MDR) in breast cancer is linked to MDR1/P-glycoprotein (P-gp) and glucosylceramide synthase (GCS).
  • Previous research indicated GCS affects MDR1 in cancer cells, but the reverse relationship was unexplored.

Purpose of the Study:

  • To investigate whether MDR1 expression influences GCS in breast cancer.
  • To elucidate the regulatory role of MDR1 on GCS and its downstream effects on apoptosis.

Main Methods:

  • Transfection of MDR1 cDNA into MCF-7 cells and MDR1 RNA interference (RNAi) into MCF-7/ADM cells.
  • Quantitative assessment of MDR1 and GCS expression using RT-PCR and Western blot.
  • Evaluation of cell viability and apoptosis via MTT assay and flow cytometry.

Main Results:

  • Upregulation of MDR1 led to increased GCS expression, while MDR1 RNAi decreased GCS levels.
  • Changes in ceramide levels were inversely correlated with GCS expression.
  • Ceramide alterations paralleled changes in the apoptosis rate.

Conclusions:

  • MDR1 positively regulates GCS expression in breast cancer cells.
  • MDR1 enhances cellular apoptosis by modulating GCS expression, suggesting a new therapeutic pathway.

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