Research of increase radiosensitivity targeting DNA repair mechanism in treatment-resistant cells

Rad 51是一种DNA损伤后同源重组中的DNA修复蛋白，抑制Rad 51可导致体外前列腺癌细胞放射敏感性增加。本研究首先利用几种反义寡核苷酸降低Rad 51蛋白的功能，并采用彗星试验（comet assay）检测Rad 51蛋白功能的变化，然后从大肠癌细胞系（HCT 116 p53+/+，p53 -/-）中筛选出几种放射抗性克隆。我们目前正在对这些亲本和辐射抗性克隆进行Rad 51抑制，另一方面，我们研究了一种新的联合治疗方法，该方法由异黄烷醇的天然产物和电离辐射组成。我们发现，异黄烷醇、染料木黄酮的处理通过促进细胞凋亡来增加放射抗性前列腺癌细胞中的放射敏感性（Asian J Androl. 2004;6（4）：285-290.）为了应用这些发现，我们研究了FDG-PET在非小细胞肺癌中作为临床模型的疗效。我们发现并报道了FDG蓄积的肿瘤表现出放射抵抗的特点，且易发生转移。（J Clin Oncol. 2005;23（6）：1136-1143）。

Inhibition of Rad51, a DNA repair protein in homologus recombination after DNA damage, leads to an increase of radiosensitivity in prostate cancer cells in vitro. In this study, we used several antisense oligonucleotide to decrease Rad51 protein function, and evaluate Rad51 dysfunction with using comet assay, which is an analysis for DNA repair ability after DNA damage.In the next step, we first established several radioresistant clones from parental colon cancer cell lines (HCT116 p53+/+, p53 -/-). We are now applying Rad51 inhibition to those sets of parental and radioresistant clones.On the other hand, we investigated an novel combination therapy, which are consisted of natural product of isoflavinol and ionizing radiation. We found that treatment of an isoflavinol, genistein, increase radiosensitivity in radioresistant prostate cancer cells by promoting apoptosis (Asian J Androl. 2004;6(4):285-290.)To apply these findings, we investigated efficacy of FDG-PET in non-small cell lung cancer as an clinical model. We found and reported that tumor in which FDG were accumulated showed radioresistant characteristics, and metastatized frequently.(J Clin Oncol. 2005;23(6): 1136-1143).