Zhu Chun-Yu, Lv Yan-Ping, Yan Deng-Feng, Gao Fu-Lian
School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China E-mail :
Asian Pac J Cancer Prev. 2013;14(11):6757-60. doi: 10.7314/apjcp.2013.14.11.6757.
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.
胃癌是世界上最常见的恶性肿瘤之一。对化疗产生多药耐药(MDR)是胃癌治疗失败的主要原因。多药耐药1/ P-糖蛋白(MDR1 / p-gp)通过ATP依赖的药物外排泵导致耐药,并在包括胃癌在内的许多实体瘤中过表达。为了研究MDR1基因敲低对耐药逆转的作用,我们在耐药胃癌细胞中使用shRNA敲低MDR1表达,并检测阿霉素(ADR)蓄积和药物敏感性的变化。两种shRNA有效抑制了SGC7901-MDR1细胞中MDR1的mRNA和蛋白表达。MDR1基因敲低明显降低了细胞内ADR的蓄积,并增加了对ADR治疗的敏感性。总之,我们的结果揭示了MDR1在耐药中的关键作用,并证实MDR1基因敲低可逆转胃癌细胞的这种表型。