摘要
AIM: To assess the putative involvement of NF-κB and proinflammatory cytokines in the pathogenesis of cancer cachexia and the therapeutic efficacy of indomethacin (IND)on cachexia.METHODS: Thirty young male BABL/c mice were divided randomly into five groups: (a) control, (b) tumor-bearing murine were inoculated subcutaneously to induce cachexia.Saline and IND were given intraperitoneally daily for 7 days from the onset of cachexia to sacrifice. Food intake and body composition were documented, serum levels of TNFα and IL-6 and activity of NF-κB in the spleen were investigated in all animals.RESULTS: Weight loss was observed in all tumor-bearing mice. By day 16, body weights of non-tumor mice were about 72 % of healthy controls (P＜0.01), and the weight of gastrocnemius was decreased by 28.7 % (P＜0.01). No difference was found between groups in food intake (P＞0.05).Gastrocnemius weight was increased markedly (P＜0.01)body weights were not significantly elevated. Tumor-bearing caused a 2-3 fold increase in serum levels of both TNF-αand IL-6 (P＜0.01). The concentration of TNF-α (P＜0.05)and IL-6 (P＜0.01) in tumor-bearing mice was reduced after of IL-6 was slightly elevated following treatment of IND 2.0tumor-bearing mice in comparison with controls in electrophoretic mobility shift assay (ENSA). NF-κB activity a higher NF-κB activity was observed in mice treated with CONCLUSION: Colon 26 adenocarcinoma cells can induce severe cancer cachexia experimentally, and the mechanism may be partially due to the enhanced TNF-αand IL-6 in tumor-bearing animals, which is controlled by NF-κB. Low dose of indomethacin alleviates the cachexia,decreases the activation of NF-κB and the serum levels of TNF-α and IL-6, and prevents body weight loss and muscle atrophy, while no further effect is gained by a higher dosage.
AIM:To assess the putative involvement of NF-κB and pro- inflammatory cytokines in the pathogenesis of cancer cachexia and the therapeutic efficacy of indomethacin (IND) on cachexia. METHODS:Thirty young male BABL/c mice were divided randomly into five groups:(a) control,(b) tumor-bearing plus saline,(c) tumor-bearing plus IND (0.25 mg·kg^(-1)),(d) tumor-bearing plus IND (0.5 mg·kg^(-1)),and (e) tumor-bearing plus IND (2 mg·kg^(-1)).Colon 26 adenocarcinoma cells of murine were inoculated subcutaneously to induce cachexia. Saline and IND were given intraperitoneally daily for 7 days from the onset of cachexia to sacrifice.Food intake and body composition were documented,serum levels of TNF- α and IL-6 and activity of NF-κB in the spleen were investigated in all animals. RESULTS:Weight loss was observed in all tumor-bearing mice.By day 16,body weights of non-tumor mice were about 72% of healthy controls (P<0.01),and the weight of gastrocnemius was decreased by 28.7% (P<0.01).No difference was found between groups in food intake (P>0.05). Gastrocnemius weight was increased markedly (P<0.01) after treatment of IND (0.5 mg·kg^(-1)),while the non-tumor body weights were not significantly elevated.Tumor-bearing caused a 2-3 fold increase in serum levels of both TNF-α and IL-6 (P<0.01).The concentration of TNF-α (P<0.05) and IL-6 (P<0.01) in tumor-bearing mice was reduced after administration of 0.5 mg·kg^(-1) IND for 7 days.But the level of IL-6 was slightly elevated following treatment of IND 2.0 mg·kg^(-1).NF-κB activation in the spleen was increased in tumor-bearing mice in comparison with controls in electrophoretic mobility shift assay (EMSA).NF-κB activity was reduced in mice treated with 0.5 mg·kg^(-1) of IND,whereas a higher NF-κB activity was observed in mice treated with 2.0 mg·kg^(-1) of IND. CONCLUSION:Colon 26 adenocarcinoma cells can induce severe cancer cachexia experimentally,and the mechanism may be partially due to the enhanced TNF-α and IL-6 in tumor-bearing animals,which is controlled by NF-κB.Low dose of indomethacin alleviates the cachexia, decreases the activation of NF-κB and the serum levels of TNF-α and IL-6,and prevents body weight loss and muscle atrophy,while no further effect is gained by a higher dosage.
