Translational Radiobiology and Molecular oncology, Applied Radiation Therapy Trinity, Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland.
Department of Urology, St James's Hospital, Dublin, Ireland.
Sci Rep. 2019 Nov 22;9(1):17325. doi: 10.1038/s41598-019-53799-7.
The exact biological mechanism governing the radioresistant phenotype of prostate tumours at a high risk of recurrence despite the delivery of advanced radiotherapy protocols remains unclear. This study analysed the protein expression profiles of a previously generated isogenic 22Rv1 prostate cancer model of radioresistance using DigiWest multiplex protein profiling for a selection of 90 signalling proteins. Comparative analysis of the profiles identified a substantial change in the expression of 43 proteins. Differential PARP-1, AR, p53, Notch-3 and YB-1 protein levels were independently validated using Western Blotting. Pharmacological targeting of these proteins was associated with a mild but significant radiosensitisation effect at 4Gy. This study supports the clinical relevance of isogenic in vitro models of radioresistance and clarifies the molecular radiation response of prostate cancer cells.
尽管采用了先进的放疗方案,但仍不清楚导致高复发风险的前列腺肿瘤具有放射抵抗表型的确切生物学机制。本研究使用 DigiWest 多重蛋白分析对先前生成的同源 22Rv1 前列腺癌放射抵抗模型进行了蛋白表达谱分析,选择了 90 种信号蛋白。对图谱的比较分析确定了 43 种蛋白的表达发生了实质性变化。使用 Western Blotting 对差异表达的 PARP-1、AR、p53、Notch-3 和 YB-1 蛋白水平进行了独立验证。这些蛋白的药物靶向与 4Gy 时的轻微但显著的放射增敏作用相关。本研究支持放射抵抗的同源体外模型的临床相关性,并阐明了前列腺癌细胞的分子辐射反应。