Prevention of cancer cachexia by pyrrolidine dithiocarbamate (PDTC) in colon 26 tumor-bearing mice.
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.
Nai
Yong-Jun
YJ
Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
Jiang
Zhi-Wei
ZW
Wang
Zhi-Ming
ZM
Li
Ning
N
Li
Jie-Shou
JS
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
D000975:Antioxidants; D015850:Interleukin-6; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D000093242:Interleukin-6 Inhibitors; C020972:pyrrolidine dithiocarbamic acid