Fig. 6: Selective upregulation of PUMA is important for cell death induced by combination treatment. | Cell Death Discovery

Fig. 6: Selective upregulation of PUMA is important for cell death induced by combination treatment.

From: The p53 activator overcomes resistance to ALK inhibitors by regulating p53-target selectivity in ALK-driven neuroblastomas

Fig. 6

a,b Induction of PUMA was potentiated by the combination of ALK inhibitors and Nutlin-3. NB39-nu cells (a) and NB1 cells (b) were treated with 1000 nM ALK inhibitor and 10 µM Nutlin-3 for 16 h. The expression of the indicated p53-target genes was determined by qRT-PCR analysis. c–e Knockdown of PUMA prevents the cell death elicited by combination treatment. NB cells were transfected with two siRNAs targeted to PUMA, then treated with 1000 nM ALK inhibitors and 10 µM Nutlin-3 for 48 h and subjected to a CytoTox GLO assay (c,d). The knockdown efficiency of PUMA by the two siRNAs was determined by immunoblot analysis (e). f Induction of PUMA is dependent on the expression of p53. NB cells were transfected siRNAs targeting p53 and then treated with 10 µM Nutlin-3 (Nut) for 16 h. An immunoblot analysis using the indicated antibodies is shown. The data show the mean ± SD (n = 3). *p < 0.05. All the experiments were repeated at least three times

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