"Results show that when you drop glucose down to human levels, metformin has an even bigger effect at standard doses. When glucose is high you need more metformin to achieve the same results," Thor says.
Thor also points out that skeptics of metformin treatment for cancer in general or breast cancer in particular frequently point to the high concentrations of metformin needed to create results in the laboratory.
"Our data helps to explain why higher doses of metformin are required to obtain anti-cancer effects when cancer cells are grown in the lab, as compared to its use in humans," Thor says.
Interestingly, "it wasn't simply that the metformin effectiveness went up as glucose came down, but that entirely new mechanisms of action were present at lower glucose levels," Thor says.
Specifically, Thor and colleagues used RNA expression arrays to discover which genes were affected by metformin at high and low glucose concentrations. At high glucose concentrations, metformin primarily affected genes involved in metabolic processes and cell proliferation; at low glucose concentrations, metformin affected genes controlling cellular process and programmed cell death.
In addition to affecting the growth of breast cancer cells, Thor and colleagues show the drug decreases the ability of breast cancer cells to move within the body a task necessary for the spread of the disease to other sites.
"An extension of this data implies that in breast cancer patients with diabetes or metabolic syndrome, metformin may less effective at the standard dose. To be effective, doctors may have to first explore glucose control or may have to use a higher dose of metformin," Thor says.
|Contact: Garth Sundem|
University of Colorado Denver