Recombinant human epidermal growth factor (rhEGF) protects radiation-induced intestine injury in murine system

Abstract

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.