P04.48 Role of the expression of protein kinase D1 and its phosphorylated forms in glioma-derived cell line exposed to modified isothiourea derivative ZKK-3 combined with hyperbaric oxygen therapy

摘要

Background Glioblastoma (GBM) is the most malignant primary tumour of the central nervous system. Its standard treatment includes surgery, radiotherapy and chemotherapy using temozolomide. Despite this, therapies still seems to be insufficient and median survival of the patients with GBM is less than 16 months. One of the main factors involved in glioma progression is the high level of tumour hypoxia, which contributes also to its resistance to treatment. In our previous studies we demonstrated that combination of hyperbaric oxygenation with novel pentabromobenzylisothiourea ZKK-3 resulted in an improvement of GBM cells oxygenation status and the reduction of their proliferation and viability in vitro. There is a high structural similarity between isothioureas and known casein kinase 2 (CK2) inhibitors. Nevertheless, ZKK-3 does not suppress CK2 expression, while it inhibits other protein kinases, including protein kinase D1 (PKD1), which promotes tumour growth and mediates detoxification of mitochondrial reactive oxygen species. The aim of this study was to assess the changes of the expression of PKD1 and its phosphorylated forms - pPKD1 (Ser 916) and pPKD1 (Ser 744/748), in glioma-derived cells treated with ZKK-3 under various oxygen conditions in vitro.