关键词: MG132, 肿瘤恶病质, TRAF6, 自噬溶酶体途径, 泛素蛋白酶体途径

Abstract: Objective To investigate the effect of protease inhibitors MG132 on skeletal muscle consumption and the expression of TRAF6, Beclin-1,MuRF1 and MAFbx in cancer cachexia. Methods Murine colon 26 adenocarcinoma cells were inoculated into male BALB/c mice to induce cancer cachexia．24 male BALB/c mice were divided into 3 groups: healthy control group(HC);cancer cachexia group (CC)and MG132 treatment group (MG). Body weight and spontaneous activity were detected. Equal amount of physiological saline and 0.1mg/kg doses of MG132 were given intraperitoneally daily to CC and MG groups, respectively, on day 12 after tumor inoculation. All mice were sacrificed on day 19. Tumor and the left gastrocnemius muscle were accurately weighed. crosscut area of gastrocnemius muscle were measured. MRNA and protein levels of TRAF6,Beclin1, MuRF1and MAFbx were detected by RT-PCR and Western blot, respectively. Results on-tumor body weight, spontaneous activity gastrocnemius muscle weight and crosscut area of CC group lower than HC group (P < 0.05), these indexes bounced significantly of MG group (P < 0.05), but still lower than the HC group (P < 0.05). The mRNA and protein expression of TRAF6, Beclin1, MuRF1and MAFbx in the gastrocnemius muscle of CC group were significantly higher HC group (P < 0.05), these indexes of MG group were significantly lower than CC group (P < 0.05).Conclusion The improvement of skeletal muscle consumption in cancer cachexia by MG132 may involve its inhibition of TAF6 expression, thus suppressing autophagy-lysosome pathway and ubiquitin-proteasome pathway.

Key words: MG132, cancer cachexia, TRAF6, autophagy-lysosome pathway, ubiquitin-proteasome pathway