Prevention of Cancer Cachexia by Pyrrolidine Dithiocarbamate (PDTC) in Colon 26 Tumor-Bearing Mice

Abstract

Background: The precise mechanism of cancer cachexia is not fully elucidated. This study was aimed to assess the effect of pyrrolidine dithiocarbamate (PDTC, an inhibitor of NFκB) on interleukin (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 various doses of PDTC (10, 50, or 100 mg/kg/d) were given intraperitoneally daily from 7 days after tumor inoculation to killing. Body weight, food intake, and tumor volume were monitored daily. Serum and tumor tissue levels of IL-6, serum biochemical indicator, and activity of NFκB in tumor tissue were investigated in all mice. Results: Significant tissue wasting was observed in all tumor-bearing mice. By day 16, carcass weights of untreated tumor-bearing mice were about 71.3% of healthy controls (p < .01), and the weights of gastrocnemius muscle and epididymal fat were lowered by 42.4% and 70.4% (p < .01), respectively. Furthermore, tumor-bearing caused a significant decrease of serum albumin, glucose, and triglyceride (p< .01) and increase of IL-6 (p < .01) in serum and tumor tissues. Administration of PDTC dose dependently inhibited the NFκB activation in tumor tissues, inhibited IL-6 synthesis of the tumor cells, and attenuated the wasting of carcass weight, gastrocnemius muscle, and epididymal fat. Tumor growth was inhibited by PDTC with 100 mg/kg (p < .05). No differences of food intake were found between groups (p > .05). Conclusions: These results suggest that PDTC, an inhibitor of NFκB, can attenuate the development of cachexia in colon 26 tumor-bearing mice through inhibition of IL-6 synthesis regulated by NFκB.

Compared with untreated tumor-bearing mice, pyrrolidine dithiocarbamate significantly decreased interleukin-6 synthesis through the inhibition of NFκB activation of the tumors and attenuated the development of cachexia.

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