Kewitz Stefanie, Kurch Lars, Volkmer Ines, Staege Martin S
Department of Pediatrics, Martin Luther University Halle-Wittenberg, Halle, 06097, Germany.
Department of Pediatric Hematology and Oncology, Justus-Liebig-University Giessen, Feulgenstr. 12, Giessen, 35392, Germany.
Tumour Biol. 2016 Jun;37(6):8229-37. doi: 10.1007/s13277-015-4705-3. Epub 2015 Dec 30.
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.
霍奇金淋巴瘤（HL）是一种淋巴系统恶性疾病。在过去几十年中，治疗方法有所改进，但仍有患者无法治愈，且该治疗伴有多种不良晚期效应。因此，我们探究了哪些基因可能与HL细胞的化疗耐药性有关。我们观察到，用氯化钴处理后，HL细胞对顺铂的耐药性增强。因此，我们分析了在含或不含氯化钴的培养基中培养的细胞之间哪些基因存在差异表达。我们发现了几个在有氯化钴存在时上调或下调的基因，它们可能参与化疗耐药性的调节。氯化钴是一种缺氧模拟剂。因此，我们检测了缺氧条件下HL细胞的化疗耐药性和基因表达，并证实了氯化钴实验的结果。综上所述，缺氧途径的激活导致HL细胞基因表达改变和耐药性产生。差异表达基因可能是未来开发抗耐药性HL治疗策略的有趣靶点。
