Journal of Parenteral and Enteral Nutrition

 

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Journal of Parenteral and Enteral Nutrition, Vol. 31, No. 1, 18-25 (2007)
DOI: 10.1177/014860710703100118

Original Communications

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

Yong-Jun Nai, MD, Zhi-Wei Jiang, MD, Zhi-Ming Wang, MD, Ning Li, MD and Jie-Shou Li, MD

From the Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China

Correspondence: Zhi-Wei Jiang, MD, Research Institute of General Surgery, Jinling Hospital, 305 Zhongshan East Road, Nanjing, Jiangsu 210002, China. Electronic mail may be sent to ptwkjzw{at}hotmail.com.

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 NF{kappa}B) 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 NF{kappa}B 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 NF{kappa}B 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 NF{kappa}B, can attenuate the development of cachexia in colon 26 tumor-bearing mice through inhibition of IL-6 synthesis regulated by NF{kappa}B.


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