HO-1 Limits the Efficacy of Vemurafenib/PLX4032 in BRAF^V600E Mutated Melanoma Cells Adapted to Physiological Normoxia or Hypoxia.

ABSTRACT: Induction of heme oxygenase 1 (HO-1) favors immune-escape in BRAF^V600 melanoma cells treated with Vemurafenib/PLX4032 under standard cell culture conditions. However, the oxygen tension under standard culture conditions (~18 kPa O₂) is significantly higher than the physiological oxygen levels encountered in vivo. In addition, cancer cells in vivo are often modified by hypoxia. In this study, MeOV-1 primary melanoma cells bearing the BRAF^V600E mutation, were adapted to either 5 kPa O₂ (physiological normoxia) or 1 kPa O₂ (hypoxia) and then exposed to 10 μM PLX4032. PLX4032 abolished ERK phosphorylation, reduced Bach1 expression and increased HO-1 levels independent of pericellular O₂ tension. Moreover, cell viability was sign

SUBMITTER: Furfaro AL 

PROVIDER: S-EPMC9219655 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature