Fig. 8: Combined MEK inhibitor and m6A inhibitor treatment effectively suppresses the growth of JMML cells.

Combined AZD6244 and SAH treatment effectively inhibits the growth of mouse leukemia cells in vitro. Leukemia cells from moribund Kras mice were cultured in 96-well plates in the presence of vehicle or various concentrations of AZD6244 and/or SAH for 5 days. A Cell viability of Kras mice BM cells treated with AZD6244 for 5 days. B Cell viability of Kras mice BM cells treated with SAH for 5 days. C Cell viability of Control mice BM cells treated with AZD6244 for 5 days. D Cell viability of Control mice BM cells treated with SAH for 5 days. E Cell viability of Kras mice BM cells treated with AZD6244 and SAH, alone or in combination for 5 days. F Synergistic effect of AZD6244 with SAH on inhibition of the survival/growth of Kras mice BM cells as determined by the HSA independent model. Mean score represents the percentage of response beyond expectation due to drug interactions. G CI values of Kras mice BM cells treated for 5 days with AZD6244 and SAH, alone or in combination, were calculated using CompuSyn. The index value less than 1 indicates synergism. H Quantification of colonies cultured with AZD6244 and SAH, alone or in combination for 7 days in methylcellulose-based medium M3234. I Cell viability of Kras mice BM cells treated with 3-Methyladenine for 24 h. J Cell viability of Control mice BM cells treated with 3-Methyladenine for 24 h. Cell number was quantified using the Cell Counting Kit-8 assay. The results are presented as mean ± SD. *P < 0.05; **P < 0.01; ***P < 0.001.