Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Anticancer Res. 2009 Nov;29(11):4409-15.
Imexon is an aziridine-containing small pro-oxidant molecule with promising antitumor activity in myeloma, lymphoma and lung and pancreatic cancer. Imexon is already in clinical trials in patients with advanced solid tumors. The present study examined the effects of imexon on H9 and Raji lymphoma cell lines in vitro when given in combination with ionizing radiation.
H9 and Raji lymphoma cells were grown in culture and exposed to imexon, radiation, or both. Cells were assessed for cell viability, glutathione content, induction of apoptosis, cell cycle distribution and also subject to Western blot analysis.
Imexon inhibited cell proliferation in a dose-dependent manner. Imexon, given for 48 h prior to irradiation at a clinically achievable dose of 40 muM, potently enhanced the cell radiosensitivity. Imexon enhanced radiation-induced apoptosis and accumulated cells in G2/M phase of the cell cycle. Imexon induced caspase-3 activation and PARP cleavage. Alterations in glutathione levels were not observed at 40 microM of imexon.
In conclusion, imexon efficiently augmented lymphoma cell radiosensitivity independently of glutathione and the underlying mechanisms include induction of apoptosis and cell cycle redistribution.
Imexon 是一种含有氮丙啶的小分子促氧化剂，在骨髓瘤、淋巴瘤以及肺癌和胰腺癌中有很好的抗肿瘤活性。Imexon 已经在晚期实体瘤患者的临床试验中进行测试。本研究探讨了 Imexon 与电离辐射联合应用于体外 H9 和 Raji 淋巴瘤细胞系的效果。
H9 和 Raji 淋巴瘤细胞在培养中生长并接受 Imexon、辐射或两者的联合处理。通过细胞活力、谷胱甘肽含量、细胞凋亡诱导、细胞周期分布评估以及 Western blot 分析来检测细胞。
Imexon 以剂量依赖性方式抑制细胞增殖。Imexon 在临床可达到的 40 μM 剂量下预先给药 48 小时，可显著增强细胞的放射敏感性。Imexon 增强了辐射诱导的细胞凋亡并使细胞周期停滞在 G2/M 期。Imexon 诱导了 caspase-3 的激活和 PARP 的切割。在 40 μM 的 Imexon 下未观察到谷胱甘肽水平的改变。
总之，Imexon 有效地增强了淋巴瘤细胞的放射敏感性，而与谷胱甘肽无关，其潜在机制包括诱导细胞凋亡和细胞周期重分布。
