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

Y.-L., SUN, G.-Y., ZHOU, K.-N., LI, P., GAO, Q.-H., ZHANG, J.-H., ZHEN, Y.-H., BAI, X.-F., ZHANG,

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.