title: Combination of apolipoprotein A1-modi liposome-doxorubicin with autophagy inhibitors overcame drug resistance in vitro.
abstract: Multidrug resistance (MDR) represents the major drawback in chemotherapy. Liposome-based approaches could reverse MDR to some extent through circumventing the active efflux effect of P-glycoprotein. However, the reverse power of liposome is very limited because the nontargeting liposome is inefficient to deliver drugs to tumor actively. Besides, autophagy could reinforce the resistance of tumor cells to the cytotoxicity of intracellular drugs. Here, liposomal doxorubicin (Lipodox) that was conjugated with apolipoprotein A1-apo-Lipodox, was employed in tumor targeting delivery of doxorubicin. In the experiments, apo-Lipodox could enter cells effectively and reverse MDR more efficiently than their nontargeting counterpart. Autophagy occurred in this process and contributed to the survival of tumor cells. Combination use of autophagy inhibitors could enhance the cytotoxicity of apo-Lipodox and reverse drug resistance to a higher degree. We propose that this strategy holds promise to overcome MDR in human cancer.
authors.affiliation: Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China.
authors.forename: Baolong
authors.initials: B
authors.lastname: Wang
authors.affiliation: The Sixth People's Hospital of Shenzhen, Shenzhen, Guangdong 201203, People's Republic of China.
authors.forename: Duo
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Fan
authors.affiliation: Eye and Ent Hospital of Fudan University.
authors.forename: Xiaozhe
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China.
authors.forename: Xunlong
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, People's Republic of China. Electronic address: fmq@fudan.edu.cn.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Feng
mesh_terms: D016632:Apolipoprotein A-I / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007624:KB Cells; D011092:Polyethylene Glycols / Q000494:pharmacology
chemical_list: D016632:Apolipoprotein A-I; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: apo-Lipodox; apoptosis; autophagy; chemotherapy; multidrug resistance