Coinhibition of G9a and DNMTs demonstrated synergistically enhanced effects in reducing tumor growth in vivo. (A) Response of the primary MM cells to A366 and AZA administrated as single agent or in combination (n = 8). (B) Schematic representation of the experimental setup used for combinatorial A366 and AZA in vivo treatment. (C) Percent tumor volume in OPM2 tumor-bearing female Balb/c nu/nu CDX mice after treatment with either the single-agent therapies DAC,A366, or the combination over 6 days. (D) Percent tumor volume at end point after 6 days of treatment in OPM2 tumor-bearing female Balb/c nu/nu CDX mice (nvehicle = 10; nA366 = 10; nDAC = 9; ncombination = 10). Statistical analysis: a linear mixed-effects model was fitted to account for random variation across replicates, followed by pairwise comparisons using Fisher least significant difference test. Comparisons were specifically performed between the vehicle group and each treatment. Values are presented with SEM. (E) In vivo percent tumor inhibition and Bliss expected mean in mice after treatment with either the single therapies or the combination. The Bliss expected mean reflects the predicted additive effect assuming independent drug action. The synergy score represents the difference between observed and expected inhibition, with positive values indicating synergistic effects. (F) Body weight of mice monitored over the 6 days of combinatorial treatment period (ncombination = 10). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. Panel 7B was created with BioRender.com. Nylund P. and Garrido-Zabala B. (2025) https://BioRender.com/q2i0r5z.
Figure 7.

Coinhibition of G9a and DNMTs demonstrated synergistically enhanced effects in reducing tumor growth in vivo. (A) Response of the primary MM cells to A366 and AZA administrated as single agent or in combination (n = 8). (B) Schematic representation of the experimental setup used for combinatorial A366 and AZA in vivo treatment. (C) Percent tumor volume in OPM2 tumor-bearing female Balb/c nu/nu CDX mice after treatment with either the single-agent therapies DAC,A366, or the combination over 6 days. (D) Percent tumor volume at end point after 6 days of treatment in OPM2 tumor-bearing female Balb/c nu/nu CDX mice (nvehicle = 10; nA366 = 10; nDAC = 9; ncombination = 10). Statistical analysis: a linear mixed-effects model was fitted to account for random variation across replicates, followed by pairwise comparisons using Fisher least significant difference test. Comparisons were specifically performed between the vehicle group and each treatment. Values are presented with SEM. (E) In vivo percent tumor inhibition and Bliss expected mean in mice after treatment with either the single therapies or the combination. The Bliss expected mean reflects the predicted additive effect assuming independent drug action. The synergy score represents the difference between observed and expected inhibition, with positive values indicating synergistic effects. (F) Body weight of mice monitored over the 6 days of combinatorial treatment period (ncombination = 10). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. Panel 7B was created with BioRender.com. Nylund P. and Garrido-Zabala B. (2025) https://BioRender.com/q2i0r5z.

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