Study of the intervention of ubiquitin-proteasome pathway on inflammation response in experimental cancer cachexia / 肠外与肠内营养

ABSTRACT

Objective: To investigate the effect of Bortezomib (an inhibitor of proteasome) on IL-6 synthesis and cachexia in colon 26 tumor bearing mice. Methods: Murine colon 26 adenocarcinoma cells were inoculated subcutaneously in male BALB/c mice to induce cachexia. Saline and three doses of Bortezomib (0.1, 0.5 and 1.0 mg/kg) were given intraperitoneally on day 6, 9, 12 and 15 after tumor inoculation and mice were sacrificed on day 16. Body weight, food intake and tumor volume were monitored daily. Serum levels of IL-6 and IL-10, tumor tissue levels of IL-6 and activity of NF-κB in tumor tissues were investigated in all animals. Results: By day 16, saline treated tumor-bearing mice showed significant body weight and carcass weight changes (P<0.01), gastrocnemius muscle wasting and epididymal fat depletion (P<0.01). Furthermore, Tumor-bearing caused a significant increase of IL-6 and IL-10 (P<0.01) in serum and IL-6 in tumor tissues. Administration of Bortezomib attenuated the wasting of carcass weight, gastrocnemius muscle and epididymal fat. Bortezomib dose dependently inhibited the NF-κB activation and IL-6 synthesis of the tumor cells, and the maximal inhibition was observed at the dose of 1.0 mg/kg (P<0.01). Bortezomib 0.5 mg/kg significantly inhibited the increase of serum IL-6 (P<0.01). Bortezomib showed significant anti-tumor effect, and tumor growth was significantly inhibited by Bortezomib with 0.5 and 1.0 mg/kg (P<0.01). Conclusion: Bortezomib can inhibit NF-κB activation, tissue wasting and cancer cachexia.