The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats.
The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats.
复制标题
VPA对增加化学致癌物诱导的大鼠骨肉瘤细胞和原代培养细胞放射敏感性的影响
DOI：
10.3390/ijms18051027
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发表时间：
2017-05-10
影响因子：
5.6
通讯作者：
Feng Z
中科院分区：
文献类型：
--
作者：
Liu G;Wang H;Zhang F;Tian Y;Tian Z;Cai Z;Lim D;Feng Z
本研究旨在探讨丙戊酸（valproic acid，VPA）对骨肉瘤及原代培养肿瘤细胞的放射增敏作用及其机制。工作系统包括骨肉瘤细胞（U2 OS）和化学致癌剂（DMBA）诱导的大鼠乳腺癌的原代培养细胞;在这项研究中使用了克隆存活，免疫荧光，荧光原位杂交（FISH）染色体畸变，彗星试验。结果发现，VPA在安全或临界安全浓度（0.5或1.0mM）时，可导致更多的电离辐射（IR）诱导的DNA双链断裂累积，增加细胞的辐射敏感性。VPA诱导的辐射敏感性与工作系统中DNA修复活性的抑制有关。此外，染色体畸变，包括染色体断裂，染色单体断裂，放射状结构显着增加VPA和IR联合治疗后。重要的是，从化学致癌剂诱导的大鼠乳腺癌组织的原代培养细胞获得的结果进一步证实了我们的研究结果。本研究的数据表明，安全剂量的VPA通过抑制DNA双链断裂修复功能，对骨肉瘤和原代培养肿瘤细胞具有放射增敏作用。
This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function.