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

FL3 sensitizes A549Res cells but not H1299 cells to cisplatin. Sub-lethal treatment with cisplatin increased Oct-3 expression in A549Res cells (pA). The synthetic flavagline FL3 sensitized A549Res cells to cisplatin as measured by DNA fragmentation (pB) and caspase 3 and 7 activation (pC), 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 (pD, E, respectively). In A549 cells, Jarid1b expression is increased upon FL3 treatment (pF). However, P53 expression is also increased upon FL3 treatment (pG, 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 (pI, J, respectively). Data represent the mean of three independent experiments. FL3 treatment was kept during all experiment for H1299 and A549Res 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.