Figure 2. p53 Activator RG Overcomes the Resistance of AML Cells Which Survived ABT Treatment.
(A) Sensitivity comparison of parental (P) and generated resistant (R) cells. The cells were treated with ABT for 48 hr. The IC50 values were calculated with Calcusyn software based on live cell numbers.
(B) Immunoblots showing Mcl-1 and Bcl-2 levels in ABT-resistant MOLM-13R and MV-4-11R cells.
(C, D) Apoptosis induction (C) and decrease of live cell numbers (D) in the MOLM-13-R and MV-4-11R resistant cells after treatment with ABT, RG, or the combination (1:1 ratio) for 48 hr.
(E) Schematic outline of the mouse model of ABT resistance (MOLM-13-R). Treatment was started after confirmation of AML engraftment on day 0 (4 days after injection).
(F) Serial bioluminescence images of mice bearing MOLM-13-R cells after treatment with vehicle, ABT, RG, or the combination.
(G) Quantification of bioluminescence emitted from the whole body of each mouse in panel F. Data represent the mean ± SD of 5 examined mice in each group.
(H) Representative immunohistochemical (IHC) staining of murine bone marrow, spleen, and liver for human CD45 antigen on day 14. Three mice from each group were sacrificed. Rare leukemic cells in tissue sections from combination-treated mice are marked by arrows.
(I) Kaplan-Meier survival curves of mice injected with MOLM-13-R cells (n = 7 per group; statistical significance was evaluated by the log-rank test).
Data in the bar/line graphs (A, C, D) represent the means of triplicate experiments. Error bars, mean ± SD. See also Figure S2.