The Experimental Study About The Influence Of Exogenous Growth Hormone And Somatostatin On The Metablism, Immumologic Function And The Growth Of Colonic Carcinoma

Colonic carcinoma is a commonly encounted malignant tumor. Traditional clinical therapy still can not give satisfactory results. Studies have been done to demonstrate that somatostatin(SS) and analogues can inhibit the hyperplasia of normal tissue and tumor cell to induce apoptosis. We wonder if exogenous growth hormone(GH) can promote malignant tumor grow and proliferate, if exogenous somatostatin can influence the immunologic function and metabolism state, if there is any contraindication of using growth hormone in patients with malignant tumor.Objective: to explore the influence of GH and SS on the immunologic function, metabolism, tumor cell proliferation and tumor growth. So we performed this study as following : The study was composed of four parts. (l)to study the influence of growth hormone and somatostatin on the CD3~+, CD4~+, CD8~+ T lymphocyte propertion and CD4~+/CD8~+ ratio in KM mouse. (2)to evaluate the influence of growth hormone and somatostatin on the GH-IGF-1 axis and serum protein levels in SD rat. (3)to evaluate the influence of growth hormone and somatostatin on the inhibit rate(IR), the distribution of cell cycle, the proliferation index(PI), the apopstosis rate andthe expression of bax, bcl-2 mRAN in human colonic carcinoma cell line HT-29. (4)to study the effect of somatostatin and growth hormone on the growth of tumor and serum protein levels in human colonic carcinoma transplanted gymnomouse body and its mechanism.Methods: (1)KM mouse were randomly divided into growth hormone(GH) group, somatostatin(SS) group, GH+SS group and control group. The CD3+, CD4+, CD8+ T lymphocyte proportion was evaluated by flow cytometer(FCM). (2)SD rat were randomly divided into growth hormone(GH) group, somatostatin(SS) group, GH+SS group and control group. The GH-IGF-1 axis was evaluated by radioimmunoassay. The serum protein levels were evaluated by biochemical assy. (3) The inhibit rate(IR) was evaluated by MTT method; the cell cycle, proliferation index(PI) and apoptosis rate were evaluated by FCM. The mRNA levels of bax and bcl-2 gene were evaluated by RT-PCR method after the colonic carcinoma cell line HT-29 was cultivated with GH and SS. (4) Human colonic carcinoma transplanted gymnomouse model were performed and were randomly divided into (1) simple tumor transplanted group; (2) GH group (3) SS group; (4) SS+GH group and (5) control group. The cell cycle, proliferation index(PI) and apoptosis rate of tumor were evaluated by FCM. The mRNA levels of bax and bcl-2 gene were evaluated by RT-PCR method. The serum protein levels were evaluated by biochemical assy.Results: (1)Exogenous growth hormone can elevate CD3~+, CD4~+, CD8~+ T lymphocyte proportion and CD4~+/CD8~+ ratio in KM mouse. While the exogenous somatostatin give the reverse results. GH+SS can not influence the CD4~+/CD8~+ ratio in KM mouse.(2)Exogenous growth hormone singly or combined with somatostatin can elevate GH-IGF-1 axis, while somatostatin can reduce GH-IGF-1 axis.(3)Exogenous growth hormone can elevate serum glucose and pre-albumin levels in SD rat. While the exogenous somatostatin give reverse results. GH+SS can not influence the levels of serum glucose and proteins in SD rat.(4)The somatostatin can restrain the proliferation of human colonic carcinoma cell line HT-29, depress PI and promote apoptosis. There is no direct influence of GH on the human colonic carcinoma cell line HT-29. The results of the SS+GH group is similar to the SS group.(5)Somatostatin can cut down bcl-2 mRNA level and elevate bax mRNA level of human colonic carcinoma cell line HT-29, while GH can not change the bcl-2 or bax mRNA levels in vitro.(6)The exogenous somatostatin can restrain the growth of transplanted tumor, the results of growth hormone group is opposed to that of somatostatin group. There is no difference between GH+SS group and simple tumor transplanted group in tumor size.(7) GH can ameliorate hypoproteinemia, while SS can aggravate hypoproteinemia caused by transplanted tumor.(8) Exogenous SS can depress PI, promote tumor cell apoptosis, while somatostatin give reverse results.(9) Exogenous GH and SS can change the bcl-2 or bax mRNA levels in vivo.Conclusion: Exogenous growth hormone can improve immunologic function, elevate GH-IGF-1 axis and ameliorate hypoproteinemia in human colonic carcinoma transplanted gymnomouse body. Growth hormone can not influence human carcinoma cell line HT-29 directly. Exogenous growth hormone can accelerate the growth of transplanted human carcinoma significantly. Exogenous somatostatin can suppress human colonic carcinoma cell line HT-29 and can inhibit the growth of transplanted human colonic carcinoma. Exogenous somatostatin can suppress immunologic function, reduce GH-IGF-1 axis and aggravate hypoproteinemia in human colonic carcinoma transplanted gymnomouse body. GH+SS can not only avoid the accelerating effect of growth hormone on tumor growth and aggravating effect of somatostatin on hypoproteinemia in human colonic carcinoma transplanted gymnomouse body but also can ameliorate hypoproteinemia in human colonic carcinoma transplanted gymnomouse body. From the consideration of metabolism and immunological functionpoint of view, it is feasible to use GH+SS as a novel measure in the treatment of malignant tumor disease.