Valproic acid inhibits Burkitt lymphoma by downregulating PFN2 expression to modulate the PI3K/AKT pathway

Burkitt lymphoma (BL) is a type of B-cell non-Hodgkin's lymphoma, which commonly occurs in children. At present, chemotherapy is the main treatment for BL, but CHOP treatment regimen has limited effectiveness, requiring precautions against central nervous system involvement and tumor lysis syndrome. Therefore, it is urgent and necessary to find effective and low toxic drugs for the treatment of BL. Valproic acid (VPA), a commercial antiepileptic drug, has been reported to have an inhibitory effect in some tumors, but whether it is effective against BL is unclear. Using CCK-8 test and flow cytometry analysis, we found that VPA could inhibit the proliferation, cell cycle, and promote apoptosis of BL cell lines (Daudi, Raji and Namalwa). Moreover, VPA had a significant inhibitory effect on Namalwa cell line-derived xenograft (CDX) in vivo, and we successfully constructed three BL patient-derived xenograft (PDX) models, and found that VPA had significant inhibitory effects on BL PDX models in vitro and in vivo. Finally, we used RNA-seq, qPCR and Western blotting to verify that VPA could inhibit the growth of BL by down-regulating PFN2 and inhibiting PI3K/AKT pathway. In conclusion, our study demonstrated that VPA was a promising candidate for BL treatment by inhibiting PFN2/PI3K/AKT pathway.