Combined treatment with GH, insulin, and indomethacin alleviates cancer cachexia in a mouse model

Abstract

Cancer-induced cachexia involves weight loss, catabolic activity, and inflammation. We have evaluated the effects of various treatments (GH, insulin (INS), indomethacin (IND), and all possible combinations) on cancer cachexia in a mouse model. BALB/c mice that were implanted with colon-26 adenocarcinoma developed cachexia in 9 days. Body weight, tumor volume, tumor-free weight, inflammatory cytokines (tumor necrosis factor-a (TNF-a), interleukin 6 (IL6)), and nutritional markers (glucose (Glu), albumin, triglycerides (TGs)) of treatment and control groups were monitored. In the cachexia group, there was a significant decrease in tumor-free bodyweight by day 11. Treatment with GHCINSCIND significantly alleviated tumor-free bodyweight reduction and cachexiainduced changes in nutritional markers and cytokines, and prolonged survival time. GHCINSCIND treatment was more effective than other treatment combinations in elevating Glu and TGs, reducing TNF-a and IL6 levels, and prolonging survival time. In conclusion, GHCINS CIND alleviated cachexia symptoms in a murine model of cancer cachexia.

New cancer cachexia rat model generated by implantation of a peritoneal dissemination-derived human stomach cancer cell line

“…Anesthetized rats were subcutaneously inoculated with either 1 ϫ 10 6 -10 7 cells/site (tumor-bearing rats) or saline alone (non-tumorbearing control rats) in the left and right flanks. The major and minor tumor axes were measured, and the tumor volume was estimated using the following equation: tumor volume (cm 3 ) ϭ major axis (cm) ϫ minor axis (cm) ϫ minor axis (cm) ϫ 1/2, and tumor volume was converted to tumor weight (mg)/mm 3 (14,17,66). Rat model characterization.…”

“…Although cachexia strongly impacts the success of therapeutic treatments, the mechanisms underlying this syndrome are not fully understood. Stomach cancer patients in particular have the highest incidence of cachexia; however, few experimental models for the study of stomach cancer cachexia have been established (4,14,66).A useful cachexia model must meet three of the following five diagnostic criteria in addition to weight loss: anorexia, decreased muscle strength, fatigue, low fat-free mass (FFM) index, and abnormal biochemistry (anemia, increased inflammatory markers, and low serum albumin) (14). Moreover, Argilés et al (1) reported that two specific indicators, anorexia and metabolic disturbances, should be identified before arriving at a diagnosis of cachexia-associated weight loss.…”

“…Although cachexia strongly impacts the success of therapeutic treatments, the mechanisms underlying this syndrome are not fully understood. Stomach cancer patients in particular have the highest incidence of cachexia; however, few experimental models for the study of stomach cancer cachexia have been established (4,14,66).…”

“…A useful cachexia model must meet three of the following five diagnostic criteria in addition to weight loss: anorexia, decreased muscle strength, fatigue, low fat-free mass (FFM) index, and abnormal biochemistry (anemia, increased inflammatory markers, and low serum albumin) (14). Moreover, Argilés et al (1) reported that two specific indicators, anorexia and metabolic disturbances, should be identified before arriving at a diagnosis of cachexia-associated weight loss.…”

“…The images were captured by a charge-coupled device camera (Dage-MTI, Michigan City, IN). Mean absorbance was measured and compared with simultaneously exposed 14 C microscale samples (Amersham). The standard curve was fitted according to the absorbance of the 14 C microscale on the same film.…”