title: 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 NFkappaB) 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 NFkappaB 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 NFkappaB 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 NFkappaB, can attenuate the development of cachexia in colon 26 tumor-bearing mice through inhibition of IL-6 synthesis regulated by NFkappaB.
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Nai
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Jiang
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jie-Shou
authors.initials: JS
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000150:complications* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002100:Cachexia / Q000209:etiology / Q000517:prevention & control*; D003110:Colonic Neoplasms / Q000150:complications* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D009368:Neoplasm Transplantation; D011759:Pyrrolidines / Q000627:therapeutic use*; D011897:Random Allocation; D013859:Thiocarbamates / Q000627:therapeutic use*; D015431:Weight Loss; D000093242:Interleukin-6 Inhibitors
chemical_list: D000975:Antioxidants; D015850:Interleukin-6; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D000093242:Interleukin-6 Inhibitors; C020972:pyrrolidine dithiocarbamic acid