Panobinostat Enhances Cytarabine and Daunorubicin Sensitivities in AML Cells through Suppressing the Expression of BRCA1, CHK1, and Rad51
Figure 4
Antileukemic activity of panobinostat alone, cytarabine alone, and panobinostat plus cytarabine in a U937 xenograft model.
NOD-SCID-IL2Rγnull (NSG) mice were injected with luciferase-labeled U937 cells and treated 3 days later with panobinostat (5 mg/kg once daily for 3 weeks), ara-C (6.25 mg/kg once daily for 4 weeks), or combination (panobinostat 5 mg/kg once daily for 3 weeks plus ara-C 6.25 mg/kg once daily for 4 weeks). Serial bioluminescence images of representative mice receiving panobinostat alone (n = 8), ara-C alone (n = 10), or panobinostat plus ara-C (n = 8) (Panel A). When bioluminescence reached 1.5×107 p/s/cm2/sr, day 17 after injection of U937 cells, mice received panobinostat (5 mg/kg once daily×2). Four hours after the second dose mice were sacrificed and Bone Marrows were harvested. Pellets were lysed and subjected to Western Blot (Panel B). Tumor progression monitored by quantitative biophotonic imaging analysis of control and treatment groups (Panel C). A plot of overall survival probability, estimated with the Kaplan–Meier method (Panel D).