Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi)

Abstract
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.