Fig. 3: The combination of BCL2 and MCL1 inhibitors is effective and synergic in HMCLs resistant to each inhibitor alone. | Cell Death & Disease

Fig. 3: The combination of BCL2 and MCL1 inhibitors is effective and synergic in HMCLs resistant to each inhibitor alone.

From: Dual targeting of BCL2 and MCL1 rescues myeloma cells resistant to BCL2 and MCL1 inhibitors associated with the formation of BAX/BAK hetero-complexes

Fig. 3

a Sensitivity of 26 HMCLs to S63845 versus venetoclax. After 24 h of treatment with increasing concentrations of S63845, cell death was assessed by Annexin V staining and LD50s were calculated from at least three independent experiments. Venetoclax LD50s were previously established9. HMCLs resistant to both BH3-mimetic are indicated in green. b JJN3, KMM1, BCN, MM1S, MM1SDR, XG11, LP1, JIM3, U266, and NAN8 were treated with increasing doses of the combination S63845/venetoclax for 24 h. Cell death was assessed by Annexin V staining. Data represent the mean of three independent experiments ± SD. Combination Index (CI) was calculated with Compusyn software, Hash represents CI < 0.4. c In vivo effect of S63845/venetoclax on tumor growth in U266 xenograft model. U266 xenografts were treated with vehicle (p.o. and i.v.), venetoclax (p.o.) (blue arrows), S63845 (i.v.) (red arrows) or venetoclax (p.o.) + S63845 (i.v.) (violet arrows) as indicated. Left panel: tumor growth was monitored by measurement of tumor volumes. Mean tumor volume ± SEM of each treatment group (six mice per group) is depicted. Statistical analysis was performed using a two-way ANOVA test, followed by a Tukey’s post-test (*p < 0.05, ***p < 0.001). Right panel: analysis of tumor volumes at day 26. Mann–Whitney test was used for statistical analysis.

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