Fig. 6: DNR and AZ10606120 combined treatment is more effective in reducing HL-60 growth in nude mice in comparison to their single administration, affecting P2X7RA, P2X7RB, and c-myc expression. | Cell Death & Disease

Fig. 6: DNR and AZ10606120 combined treatment is more effective in reducing HL-60 growth in nude mice in comparison to their single administration, affecting P2X7RA, P2X7RB, and c-myc expression.

From: Differential sensitivity of acute myeloid leukemia cells to daunorubicin depends on P2X7A versus P2X7B receptor expression

Fig. 6

a–i Female nude mice were subcutaneously inoculated into the fat of the right limb with 5 × 106 HL-60 cells. DNR (0.75 mg/kg), AZ10606120 (5 mg/kg), and both drugs combined were i.m. administered to mice at post-inoculum days 8 and 10. a, b Placebo depicted in black, DNR depicted in red, AZ10606120 depicted in green, DNR + AZ10606120 depicted in blue, n = 12 for each group. a At the indicated time points, tumor volume was in vivo assessed by a caliper. Data are represented as mean ± SEM. Significance is not depicted in the figure to increase clarity. Placebo versus DNR + AZ10606120 at day 10 P ≤ 0.0001, at day 11 P ≤ 0.01, at day 12 P ≤ 0.001. DNR versus DNR + AZ10606120 at day 10 P ≤ 0.05. AZ10606120 versus DNR + AZ10606120 at day 10 P ≤ 0.01. b Ex vivo tumor volume assessed at day 12 by a caliper. Data are represented as mean ± SEM. *P ≤ 0.05; **P ≤ 0.01; ****P ≤ 0.0001. c Representative picture of tumors from treated mice at post-inoculum day 12. d, e P2X7R isoforms A and B mRNA tumor levels were evaluated by real-time PCR as described in “Materials, subjects, and methods.” d P2X7RA mRNA expression. Data are represented as mean ± SEM. **P ≤ 0.01; ***P ≤ 0.001. e P2X7RB mRNA expression. Data are represented as mean ± SEM. **P ≤ 0.01. f P2X7RA protein (~70 kDa) expression in excised tumors was evaluated by western blot with an antibody directed against P2X7R C terminal ___domain. Gel loading control Skp-1 (~20 kDa). g P2X7RB protein (~50 kDa) expression in excised tumors was evaluated by western blot with an antibody directed against P2X7R extracellular ___domain. Gel loading control Skp-1 (~20 kDa). h Representative Immunoblot showing c-myc expression (~50 KDa) in excised tumors. Gel loading control Skp-1 (~20 kDa). i Densitometric analysis of c-myc expression in HL-60 derived tumors normalized on Skp-1 loading control. Data were obtained in three independent experiments and are relative to three different tumor masses per group. Data are represented as mean ± SEM. *P ≤ 0.05.001.

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