The Influence And Mechanism On Proliferation Of Human Gastric Cancer Cell Lines By RhGH In Vivo And In Vitro

Cancer cachexia is a complex metabolic syndrome characterized by loss of body weight,reduced food intake and severe malnutritio.Additionally,this syndrome is always associated with impaired physical function,poor responsiveness to antineoplastic therapies,decreased quality of life and increased rates of morbidity and mortality.However,conventional anticachectic therapy with nutritional support is not efficient.Therefore,it is important for patients with gastric cancer to identify new ways to overcome cancer cachexia.Currently,rhGH has been approved by the US Food and Drug Administration for use in HIV/AIDS wasting and parenteral nutrition-dependent short-bowel syndrome[13].However,rhGH is not used in patients with advanced cancers because rhGH has been associated with an increased risk of cancer.The article selects human gastric cancer cell line as the research object to discusse the effect and mechanism of rhGH on the proliferation of human gastric cancer cell lines in vivo and in vitro,in order to assessed the benefits and risks of rhGH treatment in patients with gastric cancer.The article draws the following conclusions:1.The effect of rhGH on the proliferation of cancer cells varies with the difference of GHR expression in the cell membrane.GHR can promote the proliferation of GHR-positive cell lines,but can not promote the proliferation of GHR-negative cell lines.2.In vivo studies have shown that rhGH can promote the growth of SGC-7901 transplanted tumors,which is positively correlated with the dose of rhGH,but low dose rhGH does not promote the proliferation of SGC-7901 transplanted tumors.RhGH did not promote the growth of MKN-45 transplanted tumors,and the volume of MKN-45 transplanted tumors in low-dose rhGH experimental group decreased compared with the control group,which may be the result of rhGH combined effect.3.RhGH significantly increased the phosphorylation levels of JAK2,STAT3,AKT and ERK in SGC-7901 transplanted tumors,indicating that rhGH can bind to GHR receptors on the surface of target cells,activate JAK-STAT pathway,and ultimately up-regulate the signal transduction of MAPK/ERK and PI3K/AKT pathway,and promote the proliferation of tumor cells.At the same time,rhGH significantly increased the expression of Ki-67,VEGF and CD31 in SGC-7901 transplanted tumors,indicating that rhGH can reduce the proportion of G0 phase cells in transplanted tumors and promote the formation of neovascularization.4.RhGH can promote the net weight of both tumor-bearing mice,and the effect is positively correlated with the dose of rhGH.At the same time,rhGH can up-regulate the number and activity of NK cells in peripheral blood of two kinds of tumor-bearing mice,but the effect is negatively correlated with the dose of rhGH.5.RhGH can significantly improve the nutritional status of tumor-bearing mice and activate NK immunity,but it also has the risk of promoting tumor proliferation.For GHR-negative tumors,the risk of rhGH use is lower.Choosing the appropriate rhGH dose can reduce the risk of rhGH use.