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

<p><b>A</b>. Proliferation of 143B<i>wt</i> cells cultured in the absence or presence of 5 mM metformin under normoxic (white) or hypoxic (black, 1% O<sub>2</sub>) conditions. Growth curves over time are indicated. <b>B.</b> Proliferation of 143B<i>wt</i> cells cultured under normoxia (white) or hypoxia (black, 1% O<sub>2</sub>) 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 (<i>n</i> = 10), and is representative of three independent experiments. Raw data for this figure can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002309#pbio.1002309.s007" target="_blank">S7 Data</a>.</p>