Gambogic Acid as a Non-competitive Inhibitor of ABCB1 Reverses the Multidrug Resistance of Human Epi

• 作 者: XuWang;RongxinDeng;YanLu;QinXu;MingYan;DongxiaYe;WantaoChen;
• 机 构: Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao
• 出 处: 2014全国口腔生物医学学术年会暨“西湖国际”口腔医学高峰论坛
• 发表日期: 2014年期

　　Gambogic acid (GA) is known for its anticancer activity in a phase Ⅱ clinical trial.However, the detailed molecular mechanisms of its anti-multidrug resistance remain unclear.The present was designed to study the relationship between GA and mutidrug-resistant protein ATP-binding cassette transporter B1 (ABCB1).GA dose-dependently inhibited ABCB1 activity levels in the in vitro Pgp-GIo assay system and increased the cellular accumulation of ABCB1 substrate adriamycin.Although GA had no significant influence on ABCB1 mRNA in the Realtime PCR assay, Western blot detection indicated the compound reduced ABCB1 protein levels.Further study showed the proteasome inhibitor MG-132 reversed the GA-decreased ABCB1level and prolonged half life of ABCB1.