title: Metformin Synergistically Enhances Cisplatin-Induced Cytotoxicity in Esophageal Squamous Cancer Cells under Glucose-Deprivation Conditions.
abstract: Previous studies suggest that metformin may exert a protective effect on cisplatin-induced cytotoxicity in cancer cells, and this finding has led to a caution for considering metformin use in the treatment of cancer patients. However, in this paper we provide the first demonstration that metformin synergistically augments cisplatin cytotoxicity in the esophageal squamous cancer cell line, ECA109, under glucose-deprivation conditions, which may be more representative of the microenvironment within solid tumors; this effect is very different from the previously reported cytoprotective effect of metformin against cisplatin in commonly used high glucose incubation medium. The potential mechanisms underlying the synergistic effect of metformin on cisplatin-induced cytotoxicity under glucose-deprivation conditions may include enhancement of metformin-associated cytotoxicity, marked reduction in the cellular ATP levels, deregulation of the AKT and AMPK signaling pathways, and impaired DNA repair function.
authors.affiliation: Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Bian
authors.affiliation: Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Gu
authors.affiliation: Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, China.
authors.forename: Xia
authors.initials: X
authors.lastname: He
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D004260:DNA Repair / Q000187:drug effects; D004357:Drug Synergism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008687:Metformin / Q000008:administration & dosage*; D051058:Oncogene Protein v-akt / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008687:Metformin; D051058:Oncogene Protein v-akt; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D002945:Cisplatin