title: Suppression of glucosylceramide synthase by RNA interference reverses multidrug resistance in human breast cancer cells.
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.
authors.affiliation: Department of Pathology, School of Medicine, Shandong University, 250012 Jinan, China. yanlinsunny@yahoo.com.cn
authors.forename: Y-L
authors.initials: YL
authors.lastname: Sun
authors.forename: G-Y
authors.initials: GY
authors.lastname: Zhou
authors.forename: K-N
authors.initials: KN
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Gao
authors.forename: Q-H
authors.initials: QH
authors.lastname: Zhang
authors.forename: J-H
authors.initials: JH
authors.lastname: Zhen
authors.forename: Y-H
authors.initials: YH
authors.lastname: Bai
authors.forename: X-F
authors.initials: XF
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D020868:Gene Silencing; D015316:Genetic Therapy; D005964:Glucosyltransferases / Q000378:metabolism*; D006801:Humans; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase