Department of Human Anatomy, Histology and Embryology, Xi'an Jiaotong University School of Medicine, China.
Cancer Invest. 2010 Aug;28(7):679-88. doi: 10.3109/07357907.2010.483504.
This study aimed to evaluate the radiosensitizing effect of a COX-2 inhibitor, NS398, and its mechanism in radioresistant esophageal cancer Eca109R50Gy cells. NS398 enhanced radiosensitivity of Eca109R50Gy cells, characterized by redistribution of cell cycle, inhibition of DNA-dependent protein kinase catalytic subunit expression and induction of apoptosis. NS398 also reduced phospho-AKT level, upregulated expression of Bax and both procaspase-3 and active caspase-3, and downregulated Bcl-2 expression. Finally, NS398-induced radiosensitization was partly reversed by insulin-like growth factor-1, but not by prostaglandin E2. Our results suggest that NS398 may enhance radiosensitivity of Eca109R50Gy cells through blocking AKT activation and inducing apoptosis.
本研究旨在评估 COX-2 抑制剂 NS398 的放射增敏作用及其在耐辐射食管癌细胞 Eca109R50Gy 中的机制。NS398 增强了 Eca109R50Gy 细胞的放射敏感性,表现为细胞周期重分布、DNA 依赖性蛋白激酶催化亚单位表达抑制和细胞凋亡诱导。NS398 还降低了磷酸化 AKT 水平,上调了 Bax 和 procaspase-3 及 active caspase-3 的表达,下调了 Bcl-2 的表达。最后,胰岛素样生长因子-1 部分逆转了 NS398 诱导的放射增敏作用,但前列腺素 E2 没有。我们的结果表明,NS398 可能通过阻断 AKT 激活和诱导细胞凋亡来增强 Eca109R50Gy 细胞的放射敏感性。