Objective: To assess the putative involvement of NF-kappaB and pro-inflammatory cytokines in the pathogenesis of cancer cachexia and the therapeutic efficacy of indomethacin (IND) on cachexia.
Methods: Thirty young male BALB/c mice were divided randomly into five groups: A, control; B, tumor-bearing plus saline; C, tumor-bearing plus IND (0.25 mg/kg); D, tumor-bearing plus IND (0.5 mg/kg); and E, tumor-bearing plus IND (2.0 mg/kg). 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 TNF-alpha and IL-6 levels and activity of NF-kappaB in spleen were investigated in all animals.
Results: Cachexia was observed in all tumor-bearing mice. No difference was found between groups in food intake (P > 0.05). By day 16, body weights of non-tumor mice were about 82.0% of healthy controls (P < 0.01), and the weight of gastrocnemius was decreased by 28.7% (P < 0.01). Gastrocnemius weight was increased markedly (P < 0.01) after treatment of IND (0.5 mg/kg). Tumor-bearing caused a significant increase in serum TNF-alpha and IL-6 levels (P < 0.01). The concentration of TNF-alpha (P < 0.05) and IL-6 (P < 0.01) in tumor-bearing mice was reduced after administration of 0.5 mg/kg IND for 7 days. NF-kappaB activation in the spleen was increased in tumor-bearing mice in comparison with controls. NF-kappaB activity was reduced in mice treated with IND. The maximal inhibition was observed at an dosage of 0.5 mg/kg (P < 0.01). Liner positive correlation was found between NF-kappaB activity and cytokine levels (r(TNF-alpha) = 0.918, P(TNF-alpha) = 0.028; r(IL-6) = 0.884, P(IL-6) = 0.046).
Conclusions: Cachexia induced by colon 26 adenocarcinoma cells may be partially attributed to the enhanced TNF-alpha and IL-6 levels which is controlled by NF-kappaB. IND may inhibit the activation of NF-kappaB, decrease serum TNF-alpha and IL-6 levels and thus alleviate the cachexia.