title: The Promoting Effect of Radiation on Glucose Metabolism in Breast Cancer Cells under the Treatment of Cobalt Chloride.
abstract: We aimed to investigate the influence of radiation on hypoxia-treated breast cancers cells and its underlying mechanism. We mimicked the hypoxic response in MCF-7 cells by the treatment of CoCl2. Meanwhile, hypoxic MCF-7 cells induced by CoCl2or untreated MCF-7 cells were treated with or without radiation, and then treated with or without hypoxia inducible factors-1α (HIF-1α) inhibitor. Subsequently, glucose update and lactate release rate were determined by commercial kits, as well as the expressions of HIF-1α and the glucose metabolic pathway related genes, including fructose biphoshatase 1 (FBP1), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), and isocitrate dehydrogenase 2 (IDH20) were detected by western blotting and/or RT-PCR. The results showed that glucose uptake rate and lactate release rate were increased in cells under hypoxia and/or radiation condition compared with untreated cells (p < 0.05), while the addition of HIF-1α inhibitor decreased these rates in hypoxia + radiation treated cells (p < 0.05). In addition, compared with untreated cells, the mRNA and protein levels of HIF-1α were significantly increased under hypoxia and radiation condition (p < 0.05), while which decreased after the addition of HIF-1α inhibitor (p < 0.05). Similar content changing trends (all p < 0.05) were observed in FBP1, IDH2, GLUT1, and LDHA but not HK2. In conclusion, the combination of radiation and hypoxia could promote the glucose metabolism. Furthermore, HIF-1α might inhibit the promoting effect of radiation on glycolysis in hypoxic MCF-7 cells by regulating the glucose metabolic pathway.
authors.affiliation: Department of Radiation Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150086, China.
authors.forename: Chun-Bo
authors.initials: CB
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Internal Medicine, the Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, Nangang District, Harbin, Heilongjiang Province, 150086, China.
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Pu
authors.affiliation: Department of Internal Medicine, the Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, Nangang District, Harbin, Heilongjiang Province, 150086, China. zhangyyqzh@163.com.
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Zhang
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D003035:Cobalt / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D061986:MCF-7 Cells; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D012333:RNA, Messenger; D003035:Cobalt; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D006593:Hexokinase; C018021:cobaltous chloride; D005947:Glucose
keywords: Cancer cell; Glucose metabolism; Hypoxia inducible factors-1α; Radiation; hypoxia