Effect of Gilteritinib, Metformin and Combination treatments on gene expression in MOLM13-RES cells
Here, we report that Metformin shows a striking synergistic effect with Gilteritinib in suppressing cell proliferation and promoting apoptosis and cell cycle arrest in multiple FLT3-ITD AML cell lines, including FLT3 TKI-resistant MOLM13 cells. Mechanistically, the combinational treatment synergistically suppresses Polo-like kinase 1 (PLK1) expression and phosphorylation of FLT3/STAT5/ERK/mTOR in MOLM13-RES cells. Intriguingly, our retrospective clinical analysis has unveiled a significant correlation between Metformin intake and improved survival rates among FLT3-ITD AML patients. Collectively, the cotreatment of Metformin and Gilteritinib shows robustly enhanced therapeutic efficacy in treating FLT3-mutated AML by synergistically suppressing PLK1 expression and phosphorylation of FLT3/STAT5/ERK/mTOR. Overall design: MOLM13-RES cells were cultured under standard conditions and were treated with DMSO, Gilteritinib, Metformin and Combination, respectively. Collect the four group cells after 24 hours treatment and extract total RNA. Use 10ug for next library preparation and sequencing.