Chidamide and Anlotinib Synergistically Inhibit High Grade B-Cell Lymphomas via PI3K/AKT Signaling Pathway

High-grade B-cell lymphoma with concurrent MYC and BCL2/BCL6 rearrangements (HGBL-DHL) presents a formidable challenge, often refractory and resistant to front-line immunochemotherapies, necessitating urgent exploration of novel therapeutic approaches. Herein, we unveiled a robust synergistic anti-lymphoma efficacy of chidamide and anlotinib against HGBL-DHL. The cooperative effect of cell proliferation inhibition, apoptosis induction, and cell cycle arrest were demonstrated in cell lines through Cell Counting Kit-8, and Annexin V/PI staining, respectively. Moreover, in an HGBL-DHL-xenografted mouse model, the combination therapy markedly reduced tumor burden without inducing fatal toxicity. Mechanistically, chidamide suppressed HDAC3, while anlotinib inhibited VEGFR2, leading to down-regulation of the PI3K/AKT signaling cascade. This dual suppression was by their synergistic effect. Collectively, our preclinical findings underscored the synergistic activity of chidamide and anlotinib combination against HGBL-DHL, warranting further clinical evaluation of this regimen for treating this challenging entity. TMD8 cell were treated with DMSO, chidamide, anlotinib and chidamide combined with anlotinib for 24h.The RNA from four groups of cells was extracted and subjected to RNA sequencing.