Knockdown of MDR1 Increases the Sensitivity to Adriamycin in Drug Resistant Gastric Cancer Cells

Abstract

Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multipledrug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer.Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drugefflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistantgastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drugsensitivity.Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells.MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADRtreatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1knockdown could reverse this phenotype in gastric cancer cells.