Dimethyl fumarate abrogates hepatocellular carcinoma growth by inhibiting Nrf2/Bcl-xL axis and enhances sorafenib's efficacy.

ABSTRACT: Hepatocellular carcinoma (HCC) is characterized by poor prognosis and remains a leading cause of cancer mortality worldwide. Advanced HCC is managed with several first-line therapies, including tyrosine kinase inhibitors (TKI) and immunotherapy (mAb-PD-1 and mAb-VEGF). However, the efficacy of HCC therapeutics is often short-lived. Recent studies have demonstrated that the activation of the Nrf2-Bcl-xL pathway contributes to poor prognosis in a subset of HCC patients. Here, we found that dimethyl fumarate (DMF), a drug used for treating psoriasis and multiple sclerosis, regulates the Nrf2-Bcl-xL signaling axis to inhibit HCC growth in a mice xenograft model. Mechanistically, the downregulation of the Nrf2-Bcl-xL axis led to mitochondria stress and apoptosis in vitro and in vivo. Enforced N

SUBMITTER: Faleti OD 

PROVIDER: S-EPMC12078513 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature