Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union, Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin, 300192, China.
Med Oncol. 2011 Dec;28(4):1481-7. doi: 10.1007/s12032-010-9605-1. Epub 2010 Jul 13.
Osteosarcoma is the common primary bone malignancy in children and young adults in Eastern countries. Resistance to ionizing radiation (IR) or drugs is an underlying mechanism contributing to the failure of therapy in these patients. Rad51 is the key protein of DNA homologous recombination repair. Although high expression of Rad51 is associated with enhanced resistance to DNA damage induced by chemicals and/or ionizing radiation, the relevance of Rad51 expression in osteosarcoma and its relationship with IR sensitivity and chemo-resistance is not well understood. In this study, we elucidated the possibility of using Rad51 in the treatment of human osteosarcoma in vitro. Changes in chemo- and radiation sensitivity in cultured osteosarcoma cells occurred after suppression of Rad51 expression, using a plasmid vector-mediated short hairpin RNA (shRNA) expression system. The suppression of Rad51 correlated with cell cycle arrest in the G2 phase and inhibited tumor cell proliferation. Our results suggest that Rad51 expression levels might play an important role in radiation- and chemo-sensitivity of human osteosarcoma.
骨肉瘤是东亚地区儿童和青少年常见的原发性骨恶性肿瘤。对电离辐射（IR）或药物的耐药性是导致这些患者治疗失败的一个潜在机制。Rad51 是 DNA 同源重组修复的关键蛋白。虽然 Rad51 的高表达与增强对化学物质和/或电离辐射诱导的 DNA 损伤的抵抗力有关，但 Rad51 在骨肉瘤中的表达及其与 IR 敏感性和化疗耐药性的关系尚不清楚。在这项研究中，我们阐明了使用 Rad51 体外治疗人类骨肉瘤的可能性。使用质粒载体介导的短发夹 RNA（shRNA）表达系统抑制 Rad51 表达后，培养的骨肉瘤细胞的化疗和辐射敏感性发生变化。Rad51 的抑制与 G2 期细胞周期停滞相关，并抑制肿瘤细胞增殖。我们的结果表明，Rad51 表达水平可能在人骨肉瘤的辐射和化疗敏感性中发挥重要作用。
