Metformin is a
biguanide employed in treating type II diabetes. Its potential efficacy for treating
cancer has been demonstrated epidemiologically (lower
cancer incidence in
metformin users compared with users of sulfonylureas or
insulin) and mechanistically, primarily in cell culture.
Metformin decreases the levels of
insulin-like growth factor 1 and secondarily inhibits the
mammalian target of rapamycin pathway to exhibit anticancer effects. The current study examined its
cancer preventive efficacy in multiple standard in situ arising
cancer models.
Metformin was administered orally by gavage or in the diet, at human equivalent doses, in numerous
cancer models. In the hydroxybutyl(butyl)
nitrosamine-induced model of invasive
urinary bladder cancer,
metformin (50 or 150 mg/kg
body weight/day, intragastric) was ineffective despite high urinary concentrations of
metformin.
Metformin (250 or 500 ppm in diet) failed to decrease the incidence or invasiveness of
squamous cell cancer of the tongue in a 4-nitroquinoline-1-(4NQO)-induced model. Finally, in the Min mouse model of
gastrointestinal cancer,
metformin (400 or 1,200 ppm in diet) was ineffective. Notably, a slight increase in intestinal
tumor multiplicity was observed at the higher dose. Therefore,
metformin lacked efficacy in multiple standard
cancer models in non-diabetic rodents. This lack of efficacy may discourage any large phase clinical
cancer trials in non-diabetic individuals in the absence of clear phase-II studies.