High glucose reduces metformin-induced growth suppression and apoptosis. (A) BxPC-3 and (B) MIAPaCa-2 cells were treated with or without 10 mM metformin in normal (5 mM) or high (25 mM) glucose-containing SFM for 72 h and proliferation was assessed by MTT assay. Graphs represent changes in proliferation and mean ± SE of six replicate wells are depicted. P < 0.05, two-way ANOVA with Bonferroni post hoc test. N.S., not significant. (C) BxPC-3 and (D) MIAPaCa-2 cells were treated in 1% FBS SFM with either 5 or 25 mM glucose, with or without metformin for 24 h and processed for levels of cleaved PARP as an indicator of apoptosis by Western immunoblotting. Histograms show densitometry evaluation of relative difference in cleaved PARP intensity and represent means ± SE of three independent experiments. P-values are based on two-way ANOVA with Bonferroni post hoc test. Blots shown are representative assays from three independent experiments.