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  • Title: Suppression of glucosylceramide synthase by RNA interference reverses multidrug resistance in human breast cancer cells.
    Author: Sun YL, Zhou GY, Li KN, Gao P, Zhang QH, Zhen JH, Bai YH, Zhang XF.
    Journal: Neoplasma; 2006; 53(1):1-8. PubMed ID: 16416005.
    Abstract:
    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.
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