Impact Of Chronic Restraint Stress On Splenocyte Immunity, Growth And Angiogenesis Of Mouse Forestomach Carcinoma Xenografts In Kunming Mice

BACKGROUND&OBJECTIVE: Recent study found psychosocial factors play some important roles in carcinogenesis and development of malignant tumors, but its mechanisms remain unclear. This study was to investigate the impact of chronic restraint stress on splenocyte immunity,growth and angiogenesis of mouse forestomach carcinoma(MFC) xenografts in Kunming mice, and provide evidences for the mechanisms of psychosocial factors on malignant tumors.METHODS:Chapter 1 The Establishment of Chronic Restraint Stress Model of Kuming MiceA total of 60 Kunming mice were randomized into 4 groups: normal control,restraint,tumor and tumor plus restraint group(n=15), the normal control and tumor group were regarded as control group while the restraint and tumor plus restraint group were regarded as chronic restraint stress group in data analysis. The chronic restraint stress model was established in mice of chronic restraint group, while the mice in control group were fed normally. The behavior,weight,food-intake,water-intake,immobility time in tail suspension and forced swimming test of mice in each group were observed.Chapter 2 Impact of Chronic Restraint Stress on Splenocyte Immunity and Growth of Mouse Forestomach Carcinoma Xenografts in Kunming MiceAt week 4 MFC xenografts model were established in tumor group and tumor plus restraint group. Mice were killed ten days after inoculation of MFC cells.The weight of MFC xenografts were measured,the proliferation and cytotoxicity of splenocytes were detected by MTT assay, the level of IL-2 in splenocytes culture supernants were detected by enzyme-linked immunoabsorbent assay (ELISA).Chapter 3 Impact of Chronic Restraint Stress on Angiogenesis of MFC Xenografts in Kunming MiceThe concentrations of VEGF in serum were detected by enzyme- linked immunoabsorbent assay (ELISA), the expression of VEGF and MVD in MFC xenografts were detected by immunohistochemistry.RERULTS:Chapter 1 The Establishment of Chronic Restraint Stress Model of Kuming MiceAfter 3 weeks'restraint, mice in chronic restraint group displayed depressed, sluggishness, decreasing of activity, food-intake and water-intake, bloom of color pattern, the weight was increased slowly, the immobility time in tail suspension and forced swimming test was longer than mice in normal control group.Chapter 2 Impact of Chronic Restraint Stress on Splenocyte Immunity and Growth of Mouse Forestomach Carcinoma Xenografts in Kunming MiceThe weight of MFC xenografts was 1.39±0.39g in tumor group, 2.10±0.52g in tumor plus restraint group, compared with tumor group, MFC xenografts growth faster in tumor plus restraint group, the tumor growth rate was 51.08% (Ρ<0.01);In normal control group,restraint group,tumor group,tumor plus restraint group,the stimulus index(SI) of T lymphocyte were 1.77±0.22,1.70±0.17,1.69±0.18,1.22±0.15 respectively,the SI of B lymphocyte were 1.73±0.14,1.65±0.17,1.64±0.21,1.33±0.11 respectively, the inhibition rate of MFC cell proliferation were (23.01±4.76)%,(19.47±3.70)%,(16.81±3.68)%,(7.14±5.00)% and (33.03±3.91)%,(28.34±4.58)%,(24.94±2.97)%,(13.49±7.94)% respectively when the effector/target ratio were 5∶1 and 10∶1,and the level of IL-2 in splenocytes culture supernatants were 260.03±14.96pg/ml,239.78±10.93pg/ml,238.11±13.50pg/ml,186.34±10.42pg/ml,respectively. Two factors analysis of variance revealed that both chronic restraint stress and MFC xenografts impaired the proliferation,cytotoxicity and IL-2 secretion of splenocytes, and there had interactions effect between the two factors(Ρ<0.01), the effect of chronic restraint stress was much more obvious.Chapter 3 Impact of Chronic Restraint Stress on Angiogenesis of MFC Xenografts in Kunming MiceIn normal control group,restraint group,tumor group,tumor plus restraint group,the level of VEGF in serum were 497.424±19.427 pg/ml,519.286±17.343 pg/ml,515.676±14.153 pg/ml,559.620±11.724 pg/ml,respectively. Two factors analysis of variance revealed that both chronic restraint stress and MFC xenografts can increase the level of VEGF in serum, and there had interactions effect between the two factors(Ρ<0.01), the effect of chronic restraint stress was much more obvious. The expression of VEGF and MVD in tumor and tumor plus restraint group were 0.117±0.012(OD) , 0.145±0.011(OD) and 22.87±3.68(stick),26.53±4.41(stick) respectively with prominent difference(Ρ<0.01).CLONCLUSIONS:Chapter 1 The Establishment of Chronic Restraint Stress Model of Kuming MiceThe mice in chronic restraint group displayed obvious stressed depression which can be applied for the study about relationship between splenocyte immunity and MFC xenografts in Kuming mice. Chapter 2 Impact of Chronic Restraint Stress on Splenocyte Immunity and Growth of Mouse Forestomach Carcinoma Xenografts in Kunming MiceChronic restraint stress can impaired the proliferation,cytotoxicity and IL-2 secretion of splenocytes, impair the immune function and promote the growth of MFC xenografts in mice.Chapter 3 Impact of Chronic Restraint Stress on Angiogenesis of MFC Xenografts in Kunming MiceChronic restraint stress can elevate the serum level of VEGF and induce the expression of VEGF and MVD in MFC xenografts, which can promote the growth of MFC xenografts through angiogenesis in mice.