The epigallocatechin gallate derivative Y6 reverses drug resistance mediated by the ABCB1 transporter both in vitro and in vivo

• 来源期刊: 药学学报（英文版）
• 关键词: Epigallocatechin gallate (EGCG) 5,3',4',3",4",5 "-6-O-ethyl-EGCG (Y6) Drag resistance Resistance reversal ABCB1 P-gp
• 年，卷（期）: 2019,（2）
• 页码范围: 316-323
• 页数: 8页
• 语种: 英文

摘要

Previously,we reported that Y6,a new epigallocatechin gallate derivative,is efficacious in reversing doxorubicin (DOX)-mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells.In this study,we evaluated the efficacy of Y6 in reversing drug resistance both in vitro and in vivo by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter (ABCB1 or P-glycoprotein,P-gp).Our results showed that Y6 significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates.Y6 significantly stimulated the adenosine triphosphatase activity of ABCB1.Furthermore,Y6 exhibited a higher docking score as compared with epigallocatechin gallate inside the transmembrane domain of ABCB1.In addition,in the nude mouse tumor xenograft model,Y6 (110mg/kg,intragastric administration),in combination with doxorubicin (2 mg/kg,intraperitoneal injection),significantly inhibited the growth of BEL-7404/DOX cell xenograft tumors,compared to equivalent epigallocatechin gallate.In conclusion,Y6 significantly reversed ABCB1-mediated multidrug resistance and its mechanisms of action may result from its competitive inhibition of the ABCB1 drug efflux function.