Effects of recombinant human growth hormone on tumor growth and access relevant to Janus kinase 2-signal transducer and activator of transcription 3 of human gastric carcinoma xenografts in nude mice / 中华临床营养杂志

ABSTRACT

Objective To investigate the effects of recombinant human growth hormone (rhGH) on tumor growth and tumor angiogenesis factor relevant to Janus kinase 2-signal transducer and activator of transcription 3 of human gastric carcinoma xenografts in nude mice with different expressions of growth hormone receptor (GHR).Methods Immunocytochemical method was used to pick out one GHR-positive and one GHR-negative cell line. The cells were subcutaneously injected into 26 nude mice separately, then the patterns of xenografts in nude mice with different expressions of GHR were established. The nude mice bearing two different kinds of human gastric caicinoma were equally randomized into control group, low-dose rhGH group, and high-dose rhGH group,and were treated with drugs for 14 days. Changes of tumor volumes and body weight of nude mice were record. The protein and mRN A expressions of tumor angiogenesis factor in tumor tissue were detected by RT-PCR and Western blot, respectively. Results GHR was highly expressed in SGC-7901 celk but negative in MKN-45 cells. For nude mice bearing GHR+ SGC-7901 xenografts, the tumor volumes were significantly larger in low-dose rhGH group [(1. 141 ±0. 234) cm3] and high-dose rhGH group [(2. 106 ±0. 260) cm3] than in control group [(0.612±0. 156) cm3] (P = 0. 034, P = 0. 001), and the high-dose rhGH group revealed greater effect (P =0. 043 ). Body weight was not significantly different among three groups. Compared with the control group, the mRNA expressions of tumor angiogenesis factor were significantly increased in low-does rhGH group, and the P values of GHR, Janus kinase 2, signal transducer and activator of transcription 3, vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α), fibroblast growth factor, and matrix metalloproteinases-2 (MMP-2) was 0.001, 0.011, 0.042, 0.045, 0.040, 0.002, and 0.003, respectively; however, the high-does rhGH group did not show the greater effects. The protein expressions were significantly increased in low-does rhGH group, and the P value of phosphorylation-signal transducer and activator of transcription 3, signal transducer and activator of transcription 3, VEGF, HIF-1α, and MMP-2 was 0. 015, 0.003, 0.010, 0.008,and 0. 005, respectively; furthermore, the high-does group revealed the further greater effects, and the P value of VEGF, HIF-1α, and MMP-2 was 0.012, 0.025, and 0.046, respectively. On the contrary, for nude mice bearing GHR- MKN-45 xenografts, the body weights of low-dose rhGH group [(24.94 ±0. 517) g] and high-dose rhGH group [(26.97 ±0.686) g] were significantly higher than that of control group [(22.78 ±0.418) g] (P =0. 040, P = 0.012 ) , while tumor growth as well as the expressions of mRNA and protein of tumor angiogenesis factor in tumor tissue were not significantly different Conclusions rhGH can promote tumor growth and up-regulate the expression of tumor angiogenesis factor in the GHR-highly-expressed SGC-7901 xenograft tumor model; However,such effects do not exist in GHR-negatively-expressed MKN-45 xenograft tumor model. The existence of GHR may be a key target by which rhGH influences the tumor growth and the expressions of tumor angiogenesis factor, which is probably achieved through Janus kinase 2-signal transducer and activator of transcription 3 activation.