title: The effects of recombinant human GH on promoting tumor growth depend on the expression of GH receptor in vivo.
abstract: Cancer-related malnutrition is a mortal threat to gastric carcinoma patients. However, conventional nutrition treatment is not effective for recovery. Recombinant human GH (rhGH) is widely accepted clinically to treat severe malnutrition caused by non-malignant diseases, but not approved to treat malignant diseases due to the safety concern. To explore the safety of rhGH on gastric cancer, we assessed the effect of rhGH on two tumor-bearing mice models in vivo established by human gastric adenoma cell lines of SGC-7901 and MKN-45. VEGF expression in tumor tissues was detected using immunohistochemistry. The expression of GH receptor (Ghr), Jak-2, Stat3, Vegf, Hif-1α, Fgf, and Mmp-2 was measured by RT-PCR and protein expression of STAT3, phosphorylated STAT3, VEGF, HIF-1α, and MMP-2 was measured by western blotting. The immunocytochemistry results showed that the GHR expression of SGC-7901 was strongly positive (GHR(+++)), while GHR expression of MKN-45 was regarded as negative (GHR(-)). After 14 days of rhGH treatment in SGC-7901 (GHR(+++)) tumor-bearing mice, we found that the tumor growth was significantly increased, and the expressions of downstream factors and VEGF were increased. However, in MKN-45 (GHR(-)) tumor-bearing mice, tumor growth was not significantly increased by rhGH, but tumor-free body weight was increased especially in high-dose rhGH-treated group (P<0.05). These findings suggest that the level of GHR expression is a key target that influences the effectiveness of rhGH on promoting the growth of gastric cancer and angiogenesis. rhGH may promote the activation of tumor angiogenesis factors through the Jak-2-STAT3 pathway.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Suyi
authors.initials: S
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
authors.forename: Lu
authors.initials: L
authors.lastname: Cheng
authors.forename: Ming
authors.initials: M
authors.lastname: Quan
authors.forename: Suyu
authors.initials: S
authors.lastname: Jiang
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D019382:Human Growth Hormone / Q000009:adverse effects*; D006801:Humans; D008297:Male; D044342:Malnutrition / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000209:etiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D042501:Angiogenic Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019382:Human Growth Hormone; C051815:somatotropin-binding protein