title: 2-Deoxy-d-Glucose Sensitizes Human Ovarian Cancer Cells to Cisplatin by Increasing ER Stress and Decreasing ATP Stores in Acidic Vesicles.
abstract: Cisplatin is a commonly used chemotherapeutic agent; however, the development of acquired resistance limits its application. Here, we demonstrate that 2-deoxy-d-glucose (2-DG) enhanced the antitumor effects of cisplatin in SKOV3 cells, which include inhibition of proliferation and promotion of apoptosis. Additionally, either cisplatin or 2-DG alone could upregulate the endoplasmic reticulum (ER) stress-associated protein glucose-regulated protein-78 (GRP78). Moreover, exposure to 2-DG increased the expression of GRP78 induced by cisplatin. Cisplatin also upregulated ER stress-associated apoptotic protein 153/C/EBP homology protein (CHOP) in SKOV3 cells. While treatment with 2-DG alone could not upregulate the CHOP expression, a combination of both 2-DG and cisplatin increased the protein levels of CHOP above those induced by Cisplatin alone. Finally, cisplatin mediated an increase in ATP stores within acidic vesicles, whereas 2-DG decreased this effect. These data demonstrate that 2-DG sensitizes SKOV3 cells to cisplatin by increasing ER stress and decreasing ATP stores in acidic vesicles.
authors.affiliation: School of Public Health, Jilin Medical University, Jilin, Jilin, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xie
authors.affiliation: School of Public Health, Jilin Medical University, Jilin, Jilin, People's Republic of China.
authors.forename: Linchuan
authors.initials: L
authors.lastname: Zeng
authors.affiliation: School of Public Health, Jilin Medical University, Jilin, Jilin, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Medical Examination Center, Jilin Traditional Chinese and Western Medicine Hospital, Jilin, Jilin, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yi
authors.affiliation: Medical Research Laboratory, Jilin Medical University, Jilin, Jilin, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Medical Research Laboratory, Jilin Medical University, Jilin, Jilin, People's Republic of China.
authors.forename: Shibing
authors.initials: S
authors.lastname: Liu
authors.affiliation: Medical Research Laboratory, Jilin Medical University, Jilin, Jilin, People's Republic of China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Li
authors.affiliation: Medical Research Laboratory, Jilin Medical University, Jilin, Jilin, People's Republic of China. xuye_9707@163.com.|Department of Histology and Embryology, Jilin Medical University, Jilin, Jilin, People's Republic of China. xuye_9707@163.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000143:Acids; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D004357:Drug Synergism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000143:Acids; D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D002945:Cisplatin
keywords: 2-Deoxy-d-glucose; Cisplatin, Apoptosis; Ovarian Cancer Cells