[Role of NF-kappa B in cancer cachexia].
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.
Zhou
Wei
W
Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China.
Jiang
Zhi-Wei
ZW
Jiang
Jun
J
Li
Ning
N
Li
Jie-Shou
JS
D000230:Adenocarcinoma / Q000150:complications* / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002100:Cachexia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000150:complications* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D009368:Neoplasm Transplantation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D007213:Indomethacin