131I-recombinant human EGF has antitumor effects against MCF-7 human breast cancer xenografts with low levels of EGFR

Abstract

This study investigated the inhibitory action of 131I-recombinant human EGF ( 131I-rhEGF) on MCF-7 human breast cancer tumor development in nude mice. The activity and tumor uptake of 131I-rhEGF was measured by tissue distribution assay, and its effect on tumor growth was measured by monitoring tumor size after treatment with 131I-rhEGF. Changes in tumor cell ultrastructure were observed by transmission electron microscopy (TEM), and pathological changes in tumor tissue were observed by light microscopy. The tissue distribution assay revealed that 131I-rhEGF was markedly absorbed by the tumor and reached its maximal uptake rate (16.73%ID · g −1) at 120 hours at which point the drug concentration in the tumor was 11.1-fold, 8.1-fold, and 6.6-fold higher than that in blood, liver, and kidneys, respectively. Tumor size measurements showed that tumor development was significantly inhibited by intravenously and intratumorally injected 131I-rhEGF. Tumor inhibition rates (82.0% and 80.7%, respectively) were significantly higher than those of tumors treated with 131I (7.49%) and 131I-HSA (6.91%; P < 0.05). TEM and light microscopy revealed that intravenous and intratumoral injection of 131I-rhEGF could significantly damage and ultimately kill tumor cells. Our results suggest that 131I-rhEGF suppresses development of xenografted breast cancer cells in nude mice, providing a novel candidate for receptor-mediated targeted radiotherapy.