Combination of HDAC inhibitor and PI3K inhibitor suppresses autophagy and induces apoptosis via cytoplasmic IκBα stabilization in p53-mutant diffuse large B-cell lymphoma.

ABSTRACT: p53-mutant (p53-MUT) diffuse large B-cell lymphoma (p53⁺ DLBCL) remains a treatment-refractory DLBCL subtype lacking effective therapies. In this study, we systematically validated the synergistic therapeutic potential of HDAC inhibitor chidamide and PI3K inhibitor duvelisib in p53⁺ DLBCL through cellular models, in vivo experiments, and clinical samples. The combination regimen demonstrated robust induction of apoptosis across multiple p53⁺ DLBCL cell lines and primary clinical samples. Furthermore, it effectively reduced tumor burden in xenograft mouse models and prolonged overall survival. To elucidate the underlying mechanisms, clinical DLBCL tumor specimens from patients with p53-mutated and p53-wild-type genotypes, as well as p53⁺ DLBCL cel

SUBMITTER: Yao J 

PROVIDER: S-EPMC12501026 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature