Department of Radiation Oncology, Brain Korea 21 Project for Medical Science, Yonsei University Health System, Seoul, Korea.
J Radiat Res. 2010;51(5):535-41. doi: 10.1269/jrr.09145. Epub 2010 Jul 17.
This study was to investigate whether rhEGF protects radiation induced intestine injury without compromising antitumor effect of radiation in murine system. A radiation induced intestinal injury model was established in mice by whole body irradiation. Using this model, 4 groups were set; control, rhEGF (100 µg/kg intraperitoneally), radiation (10 Gy), and a combination (rhEGF and radiation). The level of apoptosis and proliferation were analyzed by TUNEL assay and proliferation cell nuclear antigen (PCNA) immunohistochemical staining, respectively, as well as observation of survival and body weight change. A tumor growth delay assay was performed using murine syngeneic tumors; one radioresistant tumor, HCa-I and one radiosensitive tumor, MCa-K. In the radiation induced intestinal injury model, the 10 Gy group had significantly more weight loss with less number of crypt cells and higher apoptosis than the 8 Gy group. Using 10 Gy model, radioprotective effect of rhEGF was tested. Addition of rhEGF improved not only the body weight loss but also survival following radiation. It also induced suppression of apoptosis as well as increase of PCNA expression and recovery of villi. rhEGF did not enhance the tumor growth after radiation exposure in the tested tumors. These findings suggest that combination of exogenous rhEGF and radiation can be a new anticancer strategy by protecting radiation-induced intestinal injury without alleviating antitumor effect of radiation.
本研究旨在探讨表皮生长因子(rhEGF)是否可以在不影响肿瘤放射治疗效果的情况下,保护辐射诱导的肠道损伤。通过全身照射建立了辐射诱导的肠道损伤小鼠模型。利用该模型,我们设立了 4 个组:对照组、rhEGF(100µg/kg 腹腔内注射)组、辐射组(10Gy)和联合组(rhEGF 和辐射)。通过 TUNEL 检测和增殖细胞核抗原(PCNA)免疫组化染色分别分析细胞凋亡和增殖水平,并观察生存和体重变化。利用同源肿瘤进行肿瘤生长延迟试验,包括一种辐射抗性肿瘤 HCa-I 和一种辐射敏感性肿瘤 MCa-K。在辐射诱导的肠道损伤模型中,10Gy 组的体重减轻更明显,隐窝细胞数量更少,凋亡率更高。在 10Gy 模型中,我们测试了 rhEGF 的放射保护作用。rhEGF 的添加不仅改善了辐射后的体重减轻,还提高了存活率。它还抑制了细胞凋亡,增加了 PCNA 表达,并恢复了绒毛。rhEGF 并没有增强在测试肿瘤中照射后肿瘤的生长。这些发现表明,外源性 rhEGF 与放射治疗相结合可能是一种新的抗癌策略,它可以保护辐射诱导的肠道损伤,而不减轻放射治疗的抗肿瘤作用。