Research Paper Volume 13, Issue 18 pp 21914—21940

Metformin-induced chemosensitization to cisplatin depends on P53 status and is inhibited by Jarid1b overexpression in non-small cell lung cancer cells


Figure 6. FL3 sensitizes A549Res cells but not H1299 cells to cisplatin. Sub-lethal treatment with cisplatin increased Oct-3 expression in A549Res cells (p<0.05) (A). The synthetic flavagline FL3 sensitized A549Res cells to cisplatin as measured by DNA fragmentation (p<0.001) (B) and caspase 3 and 7 activation (p<0.001) (C), Treatment with 50nM of FL3 combined with cisplatin did not increase DNA fragmentation on H1299, but increased caspase 3 and 7 activation, when compared to cisplatin alone (p<0.001) (D, E, respectively). In A549 cells, Jarid1b expression is increased upon FL3 treatment (p<0.05) (F). However, P53 expression is also increased upon FL3 treatment (p<0.001) (G, H). P53 inhibition by pifithrin-μ does not protects A549Res to cisplatin-induced cell death through DNA fragmentation assay but caspase 3 and 7 activation is lowered (p<0.001) (I, J, respectively). Data represent the mean of three independent experiments. FL3 treatment was kept during all experiment for H1299 and A549Res cells.