Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany;
Clinical Cooperation Unit Molecular Radiation Oncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
In Vivo. 2021 Jan-Feb;35(1):111-117. doi: 10.21873/invivo.12238.
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.
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.
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.
The absence of radiosensitization by CK2 inhibition should be investigated in different tumour models.
背景/目的：酪蛋白激酶 2（CK2）在细胞 DNA 损伤反应中维持多种生存促进功能，在正常细胞中受到严格调控，但在癌症中升高。CK2 被认为是一种潜在的治疗靶点，其抑制已被证明与体外哺乳动物细胞的放射增敏作用有关。在这里，我们研究了 CK2 抑制在体内的潜在放射增敏作用。
用人 WiDr-xenograft 肿瘤在 BALB/c nu/nu 小鼠皮下生长，并用和不用分次照射来研究 CK2 抑制在体内的作用。使用特异性抑制剂四溴苯并三唑（TBB）进行 CK2 抑制。组织学检查包括凋亡和双链断裂的染色。
TBB 单独治疗和单独放疗均显著抑制肿瘤生长，这反映在凋亡率增加上。然而，在联合治疗中，TBB 治疗并没有增强放疗诱导的肿瘤生长抑制，尽管凋亡率增加，双链断裂的修复减少。这与之前关于体外放射增敏的数据形成鲜明对比。
应该在不同的肿瘤模型中研究 CK2 抑制的放射增敏作用。
