RGB-286638 as a radiation sensitizer

对许多癌细胞系进行的实验表明，RGB-286638对所有被测试的细胞系，包括乳腺癌细胞系、前列腺癌细胞系、神经母细胞瘤细胞系和肺癌细胞系，都是一种有效的辐射增敏剂。在多种细胞系中发现了强辐射致敏作用，当将该化合物添加到细胞中时，辐射剂量增加了近50%。我们已经证明，这些效应与处理细胞中双链DNA断裂的增加有关，并且这些断裂的修复速度较慢。死亡机制的实验表明，细胞主要死于有丝分裂灾难，这是典型的辐射诱导细胞死亡。RGB-286638对辐射的影响也在小鼠异种移植肿瘤模型中进行了测试。我们已经开始准备发表这些结果。这种化合物很有希望用于人类。

Experiments with a number of carcinoma cell lines have shown that RGB-286638 is a potent radiation sensitizer in all cell lines tested, including breast cancer cell lines, prostate cancer cell lines, neuroblastoma cell lines, and lung cancer cell lines. Potent radiation sensitization was seen in multiple cell lines, where a nearly 50% enhancement of radiation dose was achieved when the compound was added to cells. We have demonstrated that these effects correlate with increased presence of double stranded DNA breaks in treated cells, and with slower repair of these breaks. Experiments on the mechanism of death suggest that cells die predominantly by mitotic catastrophe, as is typical for radiation-induced cell death. The effects of RGB-286638 with radiation are also being tested in a mouse xenograft tumor model. We have begun preparing these results for publication. This compound holds great promise for use in humans.