Figure 6.

Synergistic effect of combining cisplatin with inhibition of the MDM2–p53 interaction. (a) Survival of TC cells after 96 h of continuous Nutlin-3 (Nut-3) treatment as indicated, in combination with increasing cisplatin concentration. IC₅₀ values are depicted for cisplatin alone as well as the combination of cisplatin with 1 μM Nutlin-3; values are the mean±S.D. (b) Increased levels of p53 and increased PARP cleavage after targeting the MDM2/p53 axis; a representative example of three independent experiments is shown. (c) Increased apoptosis after targeting the MDM2/p53 axis with either siRNA against MDM2 or Nutlin-3 (Nut-3) in combination with cisplatin; values are the mean±S.D. of three experiments; ^#P<0.05; ^*P<0.01; ^**P<0.005. (d) Following indicated treatment TC cells were harvested and Fas membrane expression has been determined by flow cytometry. Values are depicted as MFI. Values are the mean±S.D. of three experiments (e) Decreased apoptotic response after blocking of FasL, with NOK-1, in TC cells treated with the combination of cisplatin and Nutlin-3 as indicated; values are the mean±S.D. of three experiments; ^#P<0.05; ^*P<0.01; ^**P<0.005