Fig. 5: MDM2 inhibitors augmented production of Ad-delE1B progenies through p53 expression and combination suppressed tumor growth in vivo.

Wild-type (A, C) and mutated p53 cells (B) were infected with Ad-delE1B or Ad-LacZ (3 × 103 vp/cell) for 2 days, and treated with nutlin-3a (15 µM) or RG7112 (10 µM) for further 16 h in MSTO-211H or 36 h in NCI-H226. Expression of p53, E1A, and actin as a control was examined with Western blot analysis. Quantitation of virus progenies was examined with the TCID50 method. Averages and SE bars are shown (n = 3). ns not significant, *p < 0.01. C Expression of p53 was knocked down with p53 siRNA and control siRNA was used as a control. Cells transfected with siRNA were infected with Ad-delE1B for 2 days, and then treated with nutlin-3a (15µM) or RG7112 (10 µM) for further 16 h in MSTO-211H or 36 h in NCI-H226. D Ad-delE1B (1 × 1010 vp/mouse) and MDM2 inhibitors (1 mg) produced combinatory anti-tumor effects in an animal experiment. Ad-LacZ was used as a control. The data indicated individual tumor weights and an interquartile range of weights of tumors. *p < 0.01.