The Treatment Effects By Combinative Supplementation Of Formoterol, Indomethacin And Roxithromycin On Cancer Cachexia Mice

Objective To observe the effect of the Combinative Supplementation of Formoterol(FM), Indomethacin (IND)and Roxithromycin (RM) on cancer cachexia (CC) and to study the mechanism with an animal cancer cachetic model.Methods Male BALB/c mice bearing colon 26 adenocarcinoma for 9 days were served as models of cancer cachexia. The 72 models were divided randomly into nine treating groups basing on factorial design. Formoterol was used at a dose of 1 mg/kg/d, indomethacin was used at a dose of 0.5 mg/kg/d, roxithromycin was used at a dose of 50mg/kg/d. All of drugs were injected through intraperitoneal injection. FM, IND, FM and saline were given daily for 7days from the onset of cachexia to sacrifice. Physiological conditions, bodyweight and food intake were documented every day, tumor volume were documented every day after the tumors were palpable. Serum levels of cytokine and nutritional markers were detected 7 days after treatment. Data were expressed as means±SE. Statistical significance was determined by factorial design ANOVA and Student's t-test using SPSS 10.0. P<0.05 was considered statistically significant.RESULT1 Cancer cachexia model Tumors were palpable in mice initially on day4 or 5 after inoculation of tumor cells, Mice becomes listless and less move. Tumor grew about 1cm3 after 9 days. Color pattern of mice lose luster and disorderly. Their action become sluggish, they become emaciation. Body weight of mice also begins to decrease. All mice get into cancer cachexia on the 9th day. Cachexia symptoms were observed, such as obviously poor physical activity, asthenia, piloerection, pelage lost gloss and sheded.2 left gastrocnemius weight When the experiment was finished, the left gastrocnemius weight of group B was cut down to 67% of group A(P<0.05). This experiment using three-factorial analysis showed that roxithromycin, indomethacin, formoterol can increase the left gastrocnemius alone(P<0.05), Any two of the three drugs have no interaction on elevating the left gastrocnemius weight. The three drugs combinative supplementation can mostly improve the weight of left gastrocemius.3. Biochemical indicators The levels of serum Glu and Alb in B group were obvious lower than group A (p<0.05), but the levels of TG were significant higher than group A (p<0.05). Factorial analysis indicate that FM, IND, RM can decrease the levels of TG(P<0.05). Any two of the three drugs have no interaction on decrease the levels of TG(P>0.05), but the three drugs have interaction on decrease the levels of TG(P<0.05). The three drugs combinative supplementation can mostly bring down the levels of TG. About alb factorial analysis indicate that FM, IND, RM can elevate the levels of GLU(P<0.05). Any two of the three drugs have no interaction on elevate the levels of glucose(P>0.05), but the three drugs have interaction on elevating the levels of GLU(P<0.05). The three drugs combinative supplementation can mostly improve the levels of GLU. Although Alb of groups with drugs treatment were raised, no statistical significance was detected in those groups (p >0.05). Factorial analysis indicate that FM, IND, RM have no statistical difference in elevating the levels of alb(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 show that IND could decrease the levels of IL-6 (p<0.05), but FM and RM could not(p>0.05) and there are not interactions among FM , IND and RM in IL-6 level(sP>0.05). About TNF-αfactorial analysis indicate that FM, IND, RM can lower the levels of TNF-α(P<0.001. There are not only interactions between FM and RM in decreasing the levels of TNF-α, but also the three drugs have interactions in decreasing the levels of TNF-α. The three drugs combinative supplementation can mostly decrease the levels of TNF-α.Conclusion1. This experiment had established an animal model of cancer cachexia successfully that was very similar human's by inoculating BALB/c mice with colon-26.It provides contribution for further studying cancer cachexia theory foundation and efficacy of drugs in treating cancer chachexia.2. The result of body weight decreasing, metabolic disorder and the levels of IL-6,TNF-αincreasing showed that mice in cancer cachexia condition appearance significantly metabolic disorder of glucose, lipoids and albumin. It may have correlation with cytokines. It showed that the participation of cytokines probably is one of important mechanism that is lead to happen cancer cachexia.3. Three drugs: FM, IND and RM had their own positive effects on CC mice. Drugs combination in tumor-bearing mice with cancer cachexia could produce synergistic action.