Camptothecin suppresses NRF2-ARE activity and sensitises hepatocellular carcinoma cells to anticancer drugs

Menée in vitro et à l'aide de xénogreffes, cette étude montre que la camptothécine, un alcaloïde, peut inhiber la voie de signalisation NRF2-ARE et sensibiliser les cellules de carcinome hépatocellulaire aux anticancéreux

Résumé en anglais

Background : Resistance to chemotherapy is a major obstacle in the treatment of human hepatocellular carcinoma (HCC). Despite playing an important role in chemoprevention, nuclear factor erythroid 2-related factor 2 (NRF2) also contributes to chemo- and radio-resistance. The current study focusses on camptothecin as a novel NRF2 inhibitor to sensitise HCC to chemotherapy.

Methods : The expression and transcriptional activity of NRF2 in human HCC biopsies and camptothecin-treated culture cells were determined using immunostaining, western blot, reverse-transcription quantitative real-time PCR (RT–qPCR) and luciferase reporter assay. The effect of camptothecin on chemosensitivity of cancer cells was assessed in vitro and in xenografts.

Results : The expression and transcriptional activity of NRF2 were substantially elevated in HCC biopsies compared with corresponding adjacent tissues, and positively correlated with serum