Differential Effects of Recombinant Human EGF on Proliferation and Radiation Survival of Normal Fibroblast and Cancer Cell Lines

Abstract

Objective: To evaluate the effects of recombinant human epidermal growth factor (rhEGF) on proliferation and radiation survival of normal fibroblast and cancer cell lines both in vitro and in vivo. Methods: Using normal fibroblast and cancer cell lines, we evaluated the expression of EGFR, and determined their pro- liferation and survival with rhEGF alone or in combination with radiation. For the combination treatments, we applied 10 nM rhEGF and delivered single radiation doses of 0, 2, 5, and 10 Gy. In the animal study, we introduced EMT-6 cells into BALB/c mice to assay for tumor growth delay. We applied single radiation dose of 10 or 20 Gy, with or without 1.0 mg/Kg of rhEGF, three times a day, for 7 days. Results: In a dose-dependent manner, rhEGF stimulated proliferation of the normal fibroblast, but not the cancer cell lines with low or intermediate expression of EGFR. rhEGF inhibited proliferation of the cancer cell line with the highest EGFR expression. Administration of rhEGF in combination with radiation attenuated the cell killing effect of radiation in normal fibroblast, but it had no effect or even augmented the radiation effect in cancer cell lines. In the animal study, we observed no difference in tumor growth rates when rhEGF was combined with radiation compared to radiation alone. Conclusions: Our results suggested that rhEGF might be useful in preventing and/or treating radiation-induced injury without stimulating tumor growth. Mini-Abstract: rhEGF effectively stimulated proliferation and radiation recovery in normal fibroblasts without promoting the growth of tumor cells. Therefore, it might be useful in preventing and/or treating radiation-induced tissue injury.