Abstract 2273: Metformin promotes tumorigenesis in animal models of cancer prevention
Abstract
Abstract Metformin is a bi-guanidine employed in treating Type II diabetes. Epidemiologic studies have suggested that diabetics receiving metformin vs thialidizones or insulin have a lower incidence of cancer. In addition, metformin decreases levels of AMPK and IGF1; encouraging its use in both cancer prevention and therapy settings. Most preclinical studies with metformin have employed cell culture or xenografts. We examined its efficacy in multiple in situ animal cancer models. The preventive effect of Metformin administered by gavage or in the diet, at roughly the human equivalent dose (HED), was determined in four standard animal models: (1) methylnitrosourea (MNU)-induced ER+ mammary cancers; (2) MMTV-Neu ER− mammary cancers; (3) hydroxybutyl(butyl)nitrosamine (OH-BBN) induced urinary bladder cancers; and (4) Min mouse model of intestinal tumorigenesis. In the MNU model, Metformin (150 or 50 mg/Kg BW/day) was ineffective as a preventive dose; decreasing neither tumor multiplicity nor latency. Furthermore, both doses increased final tumor weights in treated rats. PK studies at the higher dose of Metformin (150 mg/kg BW/day) showed serum levels slightly higher than humans taking 1.5 g per day. In the MMTV-Neu model, dietary metformin (1200 PPM in diet) decreased the latency of tumor development as well as slightly, but insignificantly, increasing the final tumor multiplicity. Metformin (1200 ppm in diet) in the Min mouse model marginally increased the multiplicity of…
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