College of Life Science, Anhui Agricultural University, Hefei, Anhui Province, People's Republic of China.
Scientific research center, Benbu Medical college, Benbu, Anhui Province, People's Republic of China.
PLoS One. 2019 Jan 23;14(1):e0210613. doi: 10.1371/journal.pone.0210613. eCollection 2019.
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.
本研究旨在阐明 rhGH 对 MKN-45 异种移植瘤小鼠肿瘤生长、营养状况和免疫功能的联合作用及其剂量效应关系。在这项研究中,通过皮下接种 MKN-45 细胞诱导裸鼠动物模型,并每日注射 rhGH 持续 14 天。根据从人类临床剂量转换得到的等效剂量,设置了三种 rhGH 治疗剂量,包括 2IU(0.67mg)、10IU(3.35mg)和 50IU(16.75mg)/kg 体重。每隔两到三天测量一次肿瘤体积、体重和食物摄入量。rhGH 治疗 14 天后,分离并称重肿瘤。通过免疫组织化学(IHC)检测肿瘤组织中 Ki-67、血管内皮生长因子(VEGF)和 CD31 的表达水平。通过 Western blot 检测肿瘤组织中 pJAK2、JAK2、pSTAT3、STAT3、pAKT、AKT、pERK 和 ERK 的蛋白表达水平。通过荧光激活细胞分选(FACS)检测外周血单核细胞(PBMCs)中活性 NK 细胞的百分比。结果表明,rhGH 改善了 MKN-45 异种移植瘤小鼠的食物摄入,增加了体重,增强了免疫功能,但并未促进肿瘤生长。rhGH 高剂量组的 MKN-45 异种移植瘤小鼠体重增加更多,而 rhGH 低剂量组的小鼠免疫功能更强,肿瘤体积更小。