Combined Use Of Epigallocatechin-3-gallate With β-Hydroxy-β-methyl Butyrate Alleviates Cancer Cachexia In A Mouse Model

Objective To observe the effect of the combined use of Epigallocatechin-3-gallate(EGCG) and β-Hydroxy-β-methyl butyrate (HMB) on animal cancer cachexia model，and to study the mechanismMethods Male BALB／C mice bearing colon26adenocarcinoma for9days servedas models of cancer cachexia. Totally40healthy BALB/c mice were randomized into5groups: healthy control group(HC),cancer cachexia model group(CC), cancercachexia with EGCG group, cancer cachexia with HMB group, cancer cachexiawith EGCG and HMB group.Seven days after the treatment, body weight andgastrocnemius muscle were documented．Biochemical indicators, serum interleukin-6(IL-6)，and tumor necrosis factor-ɑ(TNF-ɑ), C-reactive protein（CRP）levels wereevaluated. The expression of nuclear factor-κB(NF-κB) in tumor was detected byusing immunohistochemistry. and the expression of MAFbx and MURF-1genese werevaluated in gastrocnemius by fluorescence quantitative PCR.Results1Generally condition The tumors of tumor-bearing mice could be touchedfrom4-5days after being inoculated.The tumors grown up to0.5cm3days later,whilethe tumor-bearing mice began to weak with poor physical activity， asthenia,piloerection, shedding, and non-glossy fur.9days later the weakness of tumor-bearingmice was more obviously,and the body weight were significantly lower than that ofhealthy mice（P＜0.05）,which meaned the beginning of a state of cancer cachexia.2Body weight and Food intake The body weight of mice in the five groups hadno significant difference during the beginning several days.The body weight oftumor-bearing mice began to decline on day12, and were significantly different fromthat of healthy mice（P＜0.05）.They dropped to their lowest levels on day16,nosignificant difference in all groups of tumor-bearing mice (P＞0.05).but There was asignificant difference between tumor-bearing mice and healthy mice in non-tumorbody weight (P＜0.05).There was no significant difference in daily food intake ofeach group.3Tumor volume The tumors of tumor-bearing mice could be touched from day5on.The growth speed of tumor accelerated from day9on.and the growth speed ofEGCG group, HMB group and combined treatment group were slower than that of mice treated with placebo group.On day16，All the treatment groups had a significantsmaller tumor volume than mice group with placebo respectively(P＜0.05).4gastrocnemius muscle weight There had a significant difference in the wetweight of right rear gastrocnemius muscle of each group.5Metabolic detection EGCG group, HMB group,combined treatment group andplacebo group had a significant lower level of blood Glu and a significant higherlevel of serum TG compared with healthy control group （P＜0.05）.EGCG group,HMB group,combined treatment group and placebo group had a significant lowerlevel of serum Alb compared with healthy control group（P＜0.05）.6Serum cytokines(TNF-α、IL-6、CRP) For the serum level of TNF-α、IL-6andCRP, EGCG group, HMB group,combined treatment group and placebo group werehigher than healthy control group;EGCG group, HMB group,combined treatmentgroup were higher than the placebo group;EGCG group, HMB group were higherthan the combined treatment group.7The expression of NF-κB EGCG group, HMB group,combined treatment groupwere higher than the placebo group;EGCG group, HMB group were higher than thecombined treatment group.8The expression of MAFbx and MURF-1genese EGCG group, HMBgroup,combined treatment group were higher than the placebo group;EGCG group,HMB group were higher than the combined treatment group.ConclusionThe combined treatment of EGCG with HMB is better than EGCG or HMB, itsmechanism is probably to improve skeletal muscle metabolism by synergisticallyinhibiting NF-κB pathway.