Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi).
For reversal of MDR1 gene-dependent multidrug resistance (MDR), two small interfering RNA (siRNA) constructs were designed to inhibit MDR1 expression by RNA interference. SiRNA duplexes were used to treat human pancreatic carcinoma (EPP85-181RDB) and gastric carcinoma (EPG85-257RDB) cells. In both cellular systems, siRNAs could specifically inhibit MDR1 expression up to 91% at the mRNA and protein levels. Resistance against daunorubicin was decreased to 89% (EPP85-181RDB) or 58% (EPG85-257RDB). The data indicate that this approach may be applicable to cancer patients as a specific means to reverse tumors with a P-glycoprotein-dependent MDR phenotype back to a drug-sensitive one.
Nieth
Christiane
C
Humboldt University Berlin, Charité Campus Mitte, Institute of Pathology, Schumannstr. 20/21, D-10117, Berlin, Germany.
Priebsch
Axel
A
Stege
Alexandra
A
Lage
Hermann
H
D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics; D003630:Daunorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D003630:Daunorubicin