| Objective:To observe the effect of the combination therapy of these two drugs on cancer cachexia mice and to probe the possible mechanisms.Methods:Forty male BABL/c mice (aged from 6 to 8 weeks) were divided into 5 groups by completely randomized design: A (PKRI group), B (MPA group), C (combined treatment group), D (placebo group), E (healthy control group). Animals of the previous four groups were transplanted with colon 26 adenocarcinom subcutaneously (s.c.) into the anterior subaxilla, and 12 days later the cancer cachexia models had been established. Then implement different intervention according to different requirement of each group for 7 days. Physiological conditions, bodyweight, food intake and tumor volume were observed everyday. Non-tumor bodyweight, wet weight of gastrocnemius muscle, serum levels of nutritional markers and cytokines were detected when the treatment finished. The dates were processed by SPSS 16.0. Results are presented as"mean±SD"("χ|ˉ±s") . Differences in means between groups were determined by one-way analysis of variance. Differences were considered to be significant when P values were less than 0.05 for all test items.Results:1. Generally condition The tumors of tumor-bearing mice could be touched from 4-5 days after being inoculated. The tumors growed up to 0.5 cm~3 7 days later, while the tumor-bearing mice began to weak with poor physical activity, asthenia, piloerection, shedding, and non-glossy fur. 12 days later the weekness of tumor-bearing mice was more obviously, and the bodyweight were significantly lower than that of healthy mice(P<0.05), which meaned the beginning of a state of cachxia.2. Tumor growth The tumors of tumor-bearing mice could be touched from day 5 on. The growth speed of tumor accelerated from day 8 on and the growth speed of PKRI group, MPA group and combined treatment group were slower than that of placebo group. On day 19, PKRI group and combined treatment group had a significant smaller tumor volume than placebo group (P<0.05, P<0.01 respectively). PKRI group, MPA group and combined treatment group had a significant smaller tumor weight than placebo group(P<0.05).3. Body weightThe bodyweight of mice in the five groups had no significant difference during the beginning several days. The bodyweight of tumor-bearing mice began to decline on day 12, and were significantly different from that of healthy mice(P<0.05). They dropped to their lowest levels on day 16, and then had a slight increase because of the tumor growth. On day 19, the bodyweight of PKRI group and MPA group were significantly different from that of healthy control group (P< 0.05, P < 0.01 respectively). There was a significant difference between tumor-bearing mice and healthy mice in non-tumor bodyweight (P<0.01), but no significant difference in all groups of tumor-bearing mice (P>0.05).4. Food intake and wet weight of gastrocnemius muscleThere was no significant difference in daily food intake of each group in the initial period. The daily food intake of tumor-bearing mice began to decline on day 10.The average daily food intake of PKRI group and placebo group were significantly different from that of healthy control group(P<0.01).There had a significant difference in the wet weight of left rear gastrocnemius muscle of each group.5. Biochemistry detectionPKRI group, MPA group,combined treatment group and placebo group had a significant lower level of blood Glu and a significant higher level of serum Tg compared with healthy control group(P<0.01). Furthermore, PKRI group, MPA group and combined treatment group had a significant higher level of blood Glu and a significant lower level of serum TG compared with placebo group(P<0.01). PKRI group, MPA group,combined treatment group and placebo group had a significant lower level of serum Alb compared with healthy control group(P<0.01).6. Serum cytokinesFor the serum level of TNF-@, PKRI group, MPA group,combined treatment group and placebo group were higher than healthy control group; MPA group and placebo group were higher than PKRI group; MPA group and placebo group were higher than combined treatment group(P<0.01). PKRI group, MPA group,combined treatment group and placebo group had a significant higher level of serum IL-1 compared with healthy control group(P<0.01). For the serum level of IL-6, PKRI group, MPA group,combined treatment group and placebo group were higher than healthy control group, PKRI group, MPA group and combined treatment group were lower than group D, PKRI group, and combined treatment group were lower than MPA group (P<0.01).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. PKRI mainly improves protein metabolism and inhibits tumor growth, while MPA mainly improves appetite and increases body fat. The combination therapy of these two drugs can complement each other's advantages and play a more excellent anti-cachexia effect.
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