Procaspase 3 activator compounds combined with X-ray irradiation

我们已经从伊利诺伊大学的合作者那里获得了两种procaspase 3激活剂（PAC-1和PAC-1），并获得了一组细胞系，用于在x射线照射和不照射的情况下测试化合物。对许多肉瘤细胞系进行的初步实验表明，在低密度下，它们不能形成离散的菌落，这表明评价辐射效应的金标准（菌落形成试验）不能直接应用。我们已经评估了其他几种基于磷酸化γ - h2ax组蛋白的测定方法，以量化在缺乏和存在procaspase 3激活剂的情况下辐射的影响。我们目前正在对每个肉瘤细胞系验证这些检测方法。我们计划在不久的将来继续推进和评估辐射和procaspase 3激活剂药物的任何超加性效应的细胞系面板。

We have obtained two procaspase 3 activators (PAC-1 and sPAC-1) from our collaborators at the University of Illinois, and have obtained a panel of cell lines on which to test the compounds with and without X-irradiation. Initial experiments with a number of sarcoma cell lines showed that they did not form discrete colonies when plated at low density, indicating that the gold standard evaluation of the effects of radiation (colony formation assay) could not be applied directly. We have evaluated several other assays based on phosphorylated gamma-H2AX histone proteins to quantitate the effect of radiation in both the absence and presence of procaspase 3 activators. We are currently validating these assays for each sarcoma cell line. We plan to continue forward and evaluate the panel of cell lines for any supra-additive effects of radiation and procaspase 3 activator drug in the near future.