Abstract
Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug 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 drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drug- sensitivity. 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 ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells.
Highlights
Intrinsic or acquired resistance of human tumor to multiple chemotherapeutic agents often results in the failure of the cancer therapy
Our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells
SGC7901-MDR1 cells showed low sensitivity to ADR, so it is used as a drug resistance gastric cancer cell line
Summary
Intrinsic or acquired resistance of human tumor to multiple chemotherapeutic agents often results in the failure of the cancer therapy. Multiple drug resistance (MDR) is a phenomenon of that the resistance to one drug is accompanied by cross-resistance to a whole range of drugs with different structures and mechanisms of action (Ozben, 2006). Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp), known as ABCB1, is a member of ATP-binding cassette (ABC) family of transporters that contribute to drug resistance via ATP-dependent drug efflux pumps (Leonard et al, 2003). Elevated expression MDR1 was found in many resistant tumors, including breast (O’Driscoll and Clynes, 2006a, b), lung (Cole et al, 1992) and gastric cancers (Yamauchi et al, 1992). MDR1 pumped out various different drugs from cells to reduce the intracellular drug concentration and decrease the cytotoxicity of a broad spectrum of anticancer drugs. The mechanisms of MDR development were broadly studied, efficient strategies to overcome MDR are still needed to be developed
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