title: Targeting Cellular Metabolism Chemosensitizes the Doxorubicin-Resistant Human Breast Adenocarcinoma Cells.
abstract: Metabolic energy preferentially produced by glycolysis was an advantageous metabolic phenotype of cancer cells. It is also an essential contributor to the progression of multidrug resistance in cancer cells. By developing human breast cancer MCF-7 cells resistant to doxorubicin (DOX) (MCF-7/MDR cells), the effects and mechanisms of 2-deoxy-D-glucose (2DG), a glucose analogue, on reversing multidrug resistance were investigated. 2DG significantly inhibited the viability of MCF-7/MDR cells and enhanced DOX-induced apoptosis by upregulating protein expression of AMPKα, P53, and caspase-3. The study demonstrated that energy restriction induced by 2DG was relevant to the synergistic effect of 2DG and DOX. The proteins of multidrug gene (the MDR-related protein, MRP1) and P-glycoprotein (P-gp) in MCF-7/MDR cells were downregulated after exposure to 2DG, accompanied with the suppression of the activity of ATP-dependent drug-efflux pump and transmembrane transporter, increasing the intracellular accumulation of DOX to reverse the chemoresistance in multidrug cancer cells.
authors.affiliation: Training Center of Medical Experiments, Basic Medical School, Fudan University, Shanghai 200032, China.
authors.forename: Shulan
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Oncology, Shanghai Xuhui Central Hospital, Shanghai 200031, China.
authors.forename: Rongfei
authors.initials: R
authors.lastname: Jia
authors.affiliation: Training Center of Medical Experiments, Basic Medical School, Fudan University, Shanghai 200032, China.
authors.forename: Dongju
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D055372:AMP-Activated Protein Kinases; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D053148:Caspase 3; D003847:Deoxyglucose; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D016159:Tumor Suppressor Protein p53