Combined Treatment With Iguratimod And Pyrrolidine Dithiocarbamate Alleviates Cancer Cachexia In A Mouse Model

Objective: To observe the effect of the combinative supplementation of iguratimod (T614) and pyrrolidine dithiocarbamate(PDTC) on animal cancer cachexia model and to study the mechanism.Methords: Male BALB/c mice bearing colon 26 adenocarcinoma for 9 days were served as models of cancer cachexia . Totally 40 healthy BALB/c mice were randomized into 5 groups: healthy control group(HC),cancer cachexia model group(CC), cancer cachexia with iguratimod group, cancer cachexia with pyrrolidine dithiocarbamate group, cancer cachexia with T614 and PDTC group. Body weight,food intake and tumor volume were monitored daily.When 16 day, bodyweight and gastrocnemius muscle were documented. Biochemical indicators,serum IL-6,and TNF-αlevels were evaluated.The expression of NF-κB of tumor were studied with immunohistochemistry.RESULTS:1. Generally condition Tumors were palpable in mice initially on day 4 or 5 after inoculation of tumor cells. 9 days later when tumor grew up to1 cm~3, the tumor bearing mice began to the back of the neck dark, erect, and activities off slow, reduced activity, weakness and other symptoms. To 12 days, all the performance of mice with more pronounced weakness, and weight loss, compared with the control group was significantly different (p <0.05), which entered the state of cachexia.2. Body weight and Food intake The initial days of inoculation in each group there was no significant difference, 11 days after inoculation, tumor-bearing mice were lower than the control group body weight (P <0.05). B, C, D group 13 days to reach the lowest weight, E Group Telsda to the minimum value of 12. Since then, because the tumor allows tumor growth and rapid increase in body weight of mice in each group no significant difference in terminal body weight. To 16 days, B the weight of the mice to the tumor volume decreased 77.6% (P <0.01), C, D, E to three groups of treated mice increased tumor weight (P <0.05). PDTC can inhibit tumor growth (P <0.05). Food intake between the groups was no statistical difference (P> 0.05)..3. left weight of gastrocnemius muscle C, D, E group were higher than the weight of the left gastrocnemius B group (P <0.05), while C, D, E gastrocnemius weight difference between groups was not significant (P> 0.05).4. Biochemistry detection Mice in each group before and after treatment no significant difference in serum total protein (P <0.05). Compared with the healthy group A, B, and serum albumin and blood glucose levels decreased significantly (P <0.01), triglyceride levels increased (P <0.05). 7 days after treatment, the treatment group serum albumin levels rise, but the difference was not statistically significant (P> 0.05). C, D blood glucose levels higher than the B group (P <0.05), triglyceride levels decreased (P <0.05); combined treatment group blood glucose levels were significantly higher than the E group B, C group (P <0.05), but and triglyceride levels are elevated; C, D serum albumin, blood glucose and triglyceride levels showed no statistically significant (P <0.05). .5. Serum cytokinesNot detected in normal mouse serum IL-6 activity. B tumor-bearing mice IL-6 and serum TNF-αlevels were significantly increased (P <0.05). Given 7 days after treatment, C, D, E serum levels of serum IL-6 and TNF-αlevels decreased compared with group B (P <0.05), E group were better than the level of IL-6 C, D group (P <0.05), TNF-αlevels than D group (P <0.05); C, D, E groups of serum IL-6 and TNF-αlevels was no significant difference (P > 0.05)6 Expression of NF-KB C, D, E groups can inhibit the expression of NF-κBp65 and cachexia group significantly increased nuclear translocation of p65. Among the most significant inhibitory effect of E group, and in the cachexia group had significant differences compared (P <0.05) Conclusion:1. Cancer cachexia mice had a body weight lousing and a metabolic disorder. The interaction of proinflammatory cytokines and tumor-derived factors induces cachexia.2. Inhibition NF-KB can attenuate the develop of cachexia in colon 26 tumor bearing mice. These findings suggest that a therapeutic approach combining T614 and PDTC do have complementary effect in improving outcomes of cancer cachexia.