title: 3-Methyladenine can depress drug efflux transporters via blocking the PI3K-AKT-mTOR pathway thus sensitizing MDR cancer to chemotherapy.
abstract: Multi-drug resistance (MDR) cancer is an intractable problem. Over-expression of drug efflux transporters such as ABCB1, ABCC1 and ABCG2 contributes to it, by which they pump drugs out of cells, and result in the decrease in the efficacy of chemotherapy. To reverse the cancer MDR, we used 3-methyladenine (3-MA) treatment on taxol or doxorubicin stressed MDR cell lines A2780DX5 and SGC7091R and xeno-tumor implanted mice. The results indicate that ABCB1, ABCC1 and ABCG2 were depressed, and the PI3K-AKT-mTOR pathway was blocked. Moreover, using FITC-labeled taxol as the indicator, we observed that the drug accumulation was enhanced in MDR cells and more cells were killed after 3-MA administration. Thus suggesting that 3-MA can reverse cancer MDR via depressing agent-efflux transporters.
authors.affiliation: Institute of Tumor, Medical School, Taizhou University , Taizhou , China .
authors.forename: Zhenyou
authors.initials: Z
authors.lastname: Zou
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Cheng
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Mengjie
authors.initials: M
authors.lastname: Ni
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Junjie
authors.initials: J
authors.lastname: Fu
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects*; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects*; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D000225:Adenine; D000970:Antineoplastic Agents; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C025946:3-methyladenine; C546842:MTOR protein, human
keywords: 3-Methyladenine; PI3K–AKT–mTOR pathway; drug efflux transporters; multi-drug resistance