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

抑制DNA损伤后同源重组中的DNA修复蛋白RAD51，可导致体外培养的前列腺癌细胞放射敏感性增加。在本研究中，我们使用了几种反义寡核苷酸来降低RAD51蛋白的功能，并用彗星试验来评估RAD51的功能障碍，这是一种分析DNA损伤后DNA修复能力的方法。我们现在正在对这些亲本克隆和抗辐射克隆应用RAD51抑制。另一方面，我们研究了一种新的联合疗法，该疗法由异黄醇的天然产物和电离辐射组成。我们发现，异黄醇，染料木素的治疗，增加了放射抵抗前列腺癌细胞的放射敏感性，通过促进凋亡(亚洲J安德鲁尔。2004；6(4)：285-290。)为了应用这些发现，我们调查了FDG-PET作为临床模型在非小细胞肺癌中的疗效。我们发现并报道了积聚FDG的肿瘤表现出放射抵抗的特征，并且转移频繁。2005年；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).