Felix Zwicker1,2, Henrik Hauswald3, Klaus-Josef Weber3, JÜrgen Debus3,2, Peter E Huber3,2. 1. Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; f.zwicker@dkfz.de. 2. Clinical Cooperation Unit Molecular Radiation Oncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany. 3. Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
Abstract
BACKGROUND/AIM: Casein kinase 2 (CK2) which sustains multiple pro-survival functions in cellular DNA-damage response, is strictly regulated in normal cells but elevated in cancer. CK2 is considered as a potential therapeutic target, and its inhibition has been associated with radiosensitization in mammalian cells in vitro. Here, we investigated potential radiosensitization by CK2 inhibition in vivo. MATERIALS AND METHODS: The effect of CK2 inhibition in vivo was investigated in human WiDr-xenograft tumours grown subcutaneously on BALB/c nu/nu mice with and without fractionated irradiation. CK2 inhibition was performed using the specific inhibitor tetra-bromobenzotriazole (TBB). Histological examinations included staining for apoptosis and double-strand breaks. RESULTS: Both TBB treatment alone and radiation alone significantly reduced tumour growth, which was reflected by increased apoptosis rates. However, TBB treatment did not boost radiation-induced tumour growth suppression in combined treatment, although the apoptosis rate increased and repair of double-strand breaks was reduced. This was in stark contrast to previous data on in vitro radiosensitization. CONCLUSION: The absence of radiosensitization by CK2 inhibition should be investigated in different tumour models. Copyright
BACKGROUND/AIM: Casein kinase 2 (CK2) which sustains multiple pro-survival functions in cellular DNA-damage response, is strictly regulated in normal cells but elevated in cancer. CK2 is considered as a potential therapeutic target, and its inhibition has been associated with radiosensitization in mammalian cells in vitro. Here, we investigated potential radiosensitization by CK2 inhibition in vivo. MATERIALS AND METHODS: The effect of CK2 inhibition in vivo was investigated in humanWiDr-xenograft tumours grown subcutaneously on BALB/c nu/nu mice with and without fractionated irradiation. CK2 inhibition was performed using the specific inhibitor tetra-bromobenzotriazole (TBB). Histological examinations included staining for apoptosis and double-strand breaks. RESULTS: Both TBB treatment alone and radiation alone significantly reduced tumour growth, which was reflected by increased apoptosis rates. However, TBB treatment did not boost radiation-induced tumour growth suppression in combined treatment, although the apoptosis rate increased and repair of double-strand breaks was reduced. This was in stark contrast to previous data on in vitro radiosensitization. CONCLUSION: The absence of radiosensitization by CK2 inhibition should be investigated in different tumour models. Copyright
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