title: Stimulation of the hypoxia pathway modulates chemotherapy resistance in Hodgkin's lymphoma cells.
abstract: Hodgkin's lymphoma (HL) is a malignant disease of the lymphatic system. The therapy has been improved during the last decades but there are still patients who cannot be cured, and the therapy is associated with several adverse late effects. Therefore, we asked which genes might be involved in the chemotherapy resistance of HL cells. We observed that HL cells became more resistant against cisplatin after treatment with cobalt chloride. Therefore, we analyzed which genes were differentially expressed between cells incubated in medium with or without cobalt chloride. We found several genes which were up- or downregulated in the presence of cobalt chloride and might be involved in the modulation of chemotherapy resistance. Cobalt chloride is a hypoxia-mimetic agent. Therefore, we tested chemo-resistance and gene expression of HL cells under hypoxic conditions and confirmed the results from the cobalt chloride experiments. Taken together, activation of the hypoxia pathway led to altered gene expression and drug resistance of HL cells. Differentially expressed genes might be interesting targets for the development of future treatment strategies against drug-resistant HL.
authors.affiliation: Department of Pediatrics, Martin Luther University Halle-Wittenberg, Halle, 06097, Germany. Stefanie.Kewitz@paediat.med.uni-giessen.de.|Department of Pediatric Hematology and Oncology, Justus-Liebig-University Giessen, Feulgenstr. 12, Giessen, 35392, Germany. Stefanie.Kewitz@paediat.med.uni-giessen.de.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kewitz
authors.affiliation: Department of Nuclear Medicine, University Hospital of Leipzig, Leipzig, 04109, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Kurch
authors.affiliation: Department of Pediatrics, Martin Luther University Halle-Wittenberg, Halle, 06097, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Volkmer
authors.affiliation: Department of Pediatrics, Martin Luther University Halle-Wittenberg, Halle, 06097, Germany.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Staege
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000860:Hypoxia / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D003035:Cobalt; C018021:cobaltous chloride; D002945:Cisplatin
keywords: Cobalt chloride; Drug resistance; Gene expression; Hodgkin’s lymphoma; Hypoxia