Combined effects of C225 and 125-iodine seed radiation on colorectal cancer cells.
Combined effects of C225 and 125-iodine seed radiation on colorectal cancer cells.
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C225 和 125 碘种子辐射对结直肠癌细胞的联合作用
DOI：
10.1186/1748-717x-8-219
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发表时间：
2013-09-23
期刊：
影响因子：
--
通讯作者：
Wang J
中科院分区：
文献类型：
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作者：
Liu J;Wang H;Qu A;Li J;Zhao Y;Wang J
目的：探讨抗表皮生长因子受体(EGFR)单抗C225与125I粒子照射联合治疗人结直肠癌的疗效。我们在存在和不存在100 nm C225的情况下，对LS180细胞进行了125I连续低剂量率照射。体外分析细胞的克隆形成能力、细胞增殖、细胞周期分布、细胞凋亡和分子通路。C225的增敏比约为1.4。单独使用C225和辐射治疗对细胞生长有显著的抑制作用，但联合治疗产生的抑制作用比单独使用任何一种治疗方法都要大。照射后48h，C225可增加辐射诱导的细胞凋亡率和γ-H_2AX灶阳性细胞百分率。联合处理的细胞Akt的磷酸化水平低于单纯辐射或C225处理的细胞。这些发现表明，C225使LS180细胞对125I种子辐射增敏。生长抑制是通过诱导细胞凋亡而不是细胞周期停滞来实现的。此外，我们还证实，C225通过降低DNA-PKcs和Ku70蛋白的细胞水平来损害DNA修复。此外，抑制Akt信号的激活可能与C225介导的放射增敏有关。
To characterize the effect of combined treatment of the anti-epidermal growth factor receptor (EGFR) monoclonal antibody C225 and 125-iodine (125I) seed radiation in human colorectal cancer. We treated LS180 cells with 125I continuous low dose rate radiation in the presence and absence of 100 nM C225. The clonogenic capacity, cellular proliferation, cell cycle distribution, apoptosis, and molecular pathways of the cells following the treatments were analyzed in vitro. The sensitizer enhancement ratio of C225 was approximately 1.4. Treatment with C225 and radiation alone produced significant inhibition of cell growth, but combination therapy produced greater inhibition than either treatment administered alone. C225 increased the radiation-induced apoptosis and the fraction of γ-H2AX foci positive cells at 48 h after treatment. The Akt phosphorylation level was lower in the cells receiving the combination treatment than in the cells treated with radiation or C225 alone. These findings indicate that C225 sensitizes LS180 cells to 125I seed radiation. Growth inhibition is mediated by inducing apoptosis and not cell cycle arrest. Additionally, we confirmed that C225 impairs DNA repair by reducing the cellular level of the DNA-PKcs and Ku70 proteins. Furthermore, the inhibition of Akt signaling activation may be responsible for the C225-mediated radiosensitization.