Recombinant human growth hormone (rhGH) treatment of MKN-45 xenograft mice improves nutrition status and strengthens immune function without promoting tumor growth.

Abstract

The aim of this study was to clarify the combined effects and dose-effect relationships of rhGH on tumor growth, nutrition status, and immune function in MKN-45 xenograft mice. In this study, animal models were induced in nude mice using the subcutaneous transplantation of MKN-45 cells, and rhGH was injected daily for 14 days. Three rhGH treatment dosages were set with reference to the equivalent dosage converted from human clinical dosage, including 2 IU (0.67 mg), 10 IU (3.35 mg) and 50 IU (16.75 mg) per kg body weight. The tumor volume, body weight and food intake were measured every two or three days. After 14 days of rhGH treatment, the tumors were isolated and weighed. The expression levels of Ki-67, vascular endothelial growth factor (VEGF) and CD31in tumor tissues were detected by immunohistochemistry (IHC). The protein expression levels of pJAK2, JAK2, pSTAT3, STAT3, pAKT, AKT, pERK and ERK were measured by western blotting. The percentage of active NK cells in peripheral blood mononuclear cells (PBMCs) was detected by fluorescence-activated cell sorting (FACS). The results showed that rhGH had improved the food intake, increased the body weight and strengthened the immune function of MKN-45 xenograft mice but had not promote tumor growth. MKN-45 xenograft mice treated with rhGH at a higher dosage gained more weight, while those treated with rhGH at a lower dosage showed stronger immune function and smaller tumor volume.