title: Early reduction of glucose uptake after cisplatin treatment is a marker of cisplatin sensitivity in ovarian cancer.
abstract: Cisplatin is an effective chemotherapeutic agent for ovarian cancer, but the sensitivity of cancers differs in individual cases. Because cisplatin is reported to suppress glucose uptake, we investigated the correlation between glucose uptake and sensitivity to the drug. A fluorescent derivative of D-glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl) amino]-2-deoxyglucose), was used to evaluate glucose uptake. Two ovarian cancer cell lines, SKOV-3 as a relatively resistant line and OVCAR-3 as a relatively sensitive line, were analyzed. Both cell lines had a decreased number of cells accompanied by cell death 24 h after cisplatin treatment, but not at 3 h. In contrast, glucose uptake was decreased 3 h after high-dose cisplatin treatment, which correlated with the sensitivity to the drug at 24 h. The protein levels of glucose transporter 1 (GLUT1) did not change with cisplatin treatment. In contrast, the membrane localization of GLUT1 disappeared after cisplatin treatment. Other cisplatin-resistant cell lines did not show an early decrease in glucose uptake after cisplatin treatment. The early decrease in glucose uptake and later cell death also correlated in cultured cancer cells from ovarian cancer patients. Thus, the decrease in glucose uptake at an early time point after high dose cisplatin treatment reflected cisplatin chemosensitivity in ovarian cancer cells. Measuring glucose uptake might be useful as a rapid evaluation of cisplatin chemosensitivity in ovarian cancer patients.
authors.affiliation: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Egawa-Takata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Endo
authors.forename: Masami
authors.initials: M
authors.lastname: Fujita
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ueda
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyatake
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okuyama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshino
authors.forename: Shoji
authors.initials: S
authors.lastname: Kamiura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Enomoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000032:analysis; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; D005947:Glucose; D002945:Cisplatin