Hypoxia results in adaptive resistance to the anti-proliferative effects of metformin.

A. Proliferation of 143Bwt cells cultured in the absence or presence of 5 mM metformin under normoxic (white) or hypoxic (black, 1% O2) conditions. Growth curves over time are indicated. B. Proliferation of 143Bwt cells cultured under normoxia (white) or hypoxia (black, 1% O2) in medium containing the indicated doses of metformin. Cell numbers were determined after 72 h of treatment, and are expressed relative to cell counts in control conditions. Each data point represents the mean ± SEM for each condition (n = 10), and is representative of three independent experiments. Raw data for this figure can be found in S7 Data.