Metformin Improves Carbohydrate Metabolism and Minimizes Walker Tumor Growth in Young Rats

• Grant number: 14/00300-7
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: April 01, 2014
• End date: September 30, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Cristina Cintra Gomes Marcondes
• Grantee: Maria Cristina Cintra Gomes Marcondes
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Cancer cachexia occurs in more than 50% of cancer patients and is characterized by body weight loss, particularly lean body mass. Metformin is a drug that is widely prescribed to type 2 diabetes patients, in whom studies have shown a lowered cancer risk. This study was conducted to analyze the effects of Walker 256 tumor cells on muscle glucose uptake and glycogen storage, as well as to examine the modulatory effect of metformin treatment on tumor growth and energy store in tumor-bearing rats. Wistar rats were distributed into 4 groups: control (C), metformin (M), tumor-bearing (W) and tumor-bearing treated with metformin (WM). Metformin was orally administered (33 mg/kg/day by gavage), and all animals were sacrificed when the relative tumor mass reached 10%. Metformin reduced muscle spoliation in the WM group, while the W group exhibited a 10% reduction in lean mass. The tumor mass ratio was markedly decreased in the WM group compared to the W group (23%, p < 0.05). Muscle and liver glycogen storage were significantly reduced in the W group, whereas metformin treatment led to an increase in glycogen storage in the M and WM groups. Liver alkaline phosphatase activity increased in both the tumor-bearing groups, but the WM group had 11% lower activity than the W group. Muscle GLUT4 expression increased in both the metformin-treated groups, and metformin treatment did not affect citrate synthase activity, which was decreased in both the tumor-bearing groups. These results suggest that metformin can attenuate the tumor effects on glucose metabolism and improve the host welfare, which is jeopardized during cancer cachexia. (AU)