In Vivo Evaluation of Combined CK2 Inhibition and Irradiation in Human WiDr Tumours

体内评估 CK2 抑制剂联合放射治疗对人类 WiDr 肿瘤的疗效

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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.

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