目的 探讨COX-2基因沉默对鼻咽癌C666-1细胞放射敏感性的影响.方法 以稳定沉默COX-2基因表达的鼻咽癌Anti-COX-2 C666-1细胞和对照细胞Anti-GL-2 C666-1为研究对象,采用克隆形成实验及曲线拟合计算不同剂量辐射后各放射生物学参数和放射增敏比;采用流式细胞仪检测辐射后细胞周期的变化;采用体内荷瘤裸鼠动物模型检测放疗后皮下移植瘤的生长曲线,并计算抑瘤率.结果 Anti-COX-2 C666-l细胞SF2、D0、Dq值较对照组均明显偏低,α/β显著增高,放射增敏比为1.4014;COX-2沉默后降低了辐射诱导的G2/M期阻滞,并增加辐射后荷瘤裸鼠的抑瘤率.结论 COX-2基因稳定沉默后可改变鼻咽癌C666-1的放射生物学参数,并降低辐射引起的G2/M期阻滞,增大抑瘤率,能够起到放疗增敏的作用.%Objective To evaluate the effect of COX-2 silencing on the radiosensitivity of a nasopharyngeal carcinoma (NPC) cell line C666-1. Methods Anti-COX-2 C666-1 cell line with COX-2 gene silencing mediated by shRNAmir lentiviral vector and the control cell line Anti-GL-2 C666-1 were exposed to various radiation doses. The clonogenic survival assay and curve fitting was used to calculate the radiobiological parameters and the sensitization enhancement ratio after the radiation. Cell cycle changes were assessed after the exposure by flow cytometric analysis. In a BALB/c nude mouse model, the growth curve of the xenografts was generated and the tumor growth inhibition rate was calculated. Results Compared with the control cells, Anti-COX-2 C666-1 cells showed obviously lowered values of SF2, DO and Dq but significantly increased α/β with a sensitivity enhancement ratio of 1.4014. COX-2 gene silencing increased the inhibition rate of the tumor xenografts after the radiation, and caused also decreased percentage of G2/M arrest resulting from the exposure. Conclusion Stable COX-2 silencing in NPC cells can improve the effect of radiotherapy both in vitro and in vivo. By changing the radiobiological parameters, genetically based COX-2 inhibitor may be a potentially promising radiosensitizer of NPC.
展开▼
