The Treatment Effects By Combinative Supplementa-tion Of Growth Hormone, Insulin And Indomethacin On Cancer Cachexia Mice

Objective This study was aimed to investigate the combinative supplementation treatment effects of the growth hormone (GF) , the insulin (IN) and indomethacin (IND) on the mice with cancer cachexia.Methods Male BALB/c mice bearing colon 26 adenocarcinom for 9 days were served as models of cancer cachexia.The 138 models were divided randomly into nine treating groups basing on factorial design (control group contain ten mice,others contain sixteen mice each group): group A with GF(0.5mg/kg/d);B with IN( 0.5u/kg/d ) ;C with IND ( 0.5mg/kg/d ) ; D with GF plus IN(0.5mg/kg/d+0.5u/kg/d);E with GF plus IND(0.5mg/kg/d+0.5mg/kg/d);Fwith IN plus IND(0.5u/kg/d +0.5mg/kg/d) ; G with GF plus IN plus IND (0.5mg/kg/d+0.5u/kg/d +0.5mg/kg/d);H with saline.All of drugs was injected through intraperitoneal injection. GF,IN,IND and saline were given daily for 7days from the onset of cachexia to sacrifice. In addition, group I is normal mice(10) as normal control group. Physiological conditions and food intake were documented every day and bodyweight every two days. Serum levels of cytokine and nutritional markers were detected seven days after treatment. Data were expressed as means±SE.Statistical significance was determined by factorial design ANOVA and Student's t-test using SPSS 11.5. P<0.05 was considered statistically significant.RESULT1 Cancer cachexia model: Tumors were palpable in mice initially on day 5 after inoculation of tumor cells,symptoms of cachexia began 3-4 days later.Weight loss began once a tumor grew to 1cm3 and a rapid loss of body weight occurred. On day 9, all transplanted mice accessed to cachexia state. Cachexia symptoms were observed,such as obviously poor physical activity, obviously body weight lossing comparing with normal mice(p<0.05), asthenia, piloerection, pelage lost gloss and sheded. 2 Carcass weight Carcass weight began to degrade from day 5 and decrease obviously on day 9 which is lower than weight of group I mice(p<0.05).There were no difference between all CC groups.Carcass weight of all groups,except groups H, were more or less elevated in which that of group G was of the most increase and higher than that of other CC groups.In contrast , group H has a still carcass weight lossing . The results from ANOVA show that the carcass weight could be increased by supplementation of growth hormone(p<0.05) , insulin(p<0.05) and indomethacin (p<0.05) respectively there is interaction among growth hormone , insulin and indomethacin but are not between any two of the three(p<0.05).3 Biochemical indicators On day 16, Glu,Alb and Tg in group H were lower than those in group I (p<0.05).After treatment,comparing with group H,Glu in groups A,B,C,E,F,G were elevated(p<0.05),in which that in group G were most elevated and differed from other groups significantly(p<0.05),and there were no significant difference between other groups; Tg in groups B,C,E,F,G were higher than that in group H (p<0.05),in which group G was the highest of them(p<0.05) ; Although Alb of groups with drugs treatment were raised, no statistical significance was detected in those groups(p >0.05)4 Serum cytokines levels Comparing with normal mice, the cytokines TNF-αand IL-6 levels were raised significantly(p<0.05). After treatment with drugs, the results from ANOVA show that showed insulin and indomethacin could decrease TNF-αand IL-6 levels(p<0.05) but growth hormone could not(p>0.05).there are not interactions among growth hormone , insulin and indomethacin in TNF-αand IL-6 levels, in which there are not interactions between the two of three in TNF-α(p>0.05), and there is interaction in IL-6between insulin and indomethacin(p<0.05) but are not interactions between growth hormone and insulin or indomethacin and no interactions in combing three drugs(p>0.05).5 Survival time The mean survial time of group H was 25.83±1.94 days. Growth hormone , insulin and indomethacin could make mean survival time of tumor-bearing mice prolong after drugs treatment (p<0.05), in which there is interaction in combing three drugs (p<0.05) but not between any two of the three(p>0.05).Conclusion1 In cancer cachexia model,there are some frequent indexes such as body weight wasting,nutrition exhausting, metabolic disorder and so on.The high levels of serum cytokines IL-6,TNF-αetc are possibly associated with cancer cachexia.It is probably one of the most important mechanisms that lead to cancer cachexia.2 Three drugs: growth hormone , insulin and indomethacin had their own positive effects to CC mice. Drugs combinationin in tumor-bearing mice with cancer cachexia could produce synergistic action.The treatment effects outstripped single alone obviously and could make them obtain longer survival time.