Bortezomib induces Rho-dependent hyperpermeability of endothelial cells synergistically with inflammatory mediators.

ABSTRACT:

Background

Bortezomib (BTZ), a selective 26 S proteasome inhibitor, is clinically useful in treating multiple myeloma and mantle cell lymphoma. BTZ exerts its antitumor effect by suppressing nuclear factor-B in myeloma cells, promoting endothelial cell apoptosis, and inhibiting angiogenesis. Despite its success, pulmonary complications, such as capillary leak syndrome of the vascular hyperpermeability type, were reported prior to its approval. Although the incidence of these complications has decreased with the use of steroids, the underlying mechanism remains unclear. This study aims to investigate how BTZ influences endothelial cell permeability.

Methods

We examined the impact of BTZ on vascular endothelial cells, focusing on its effects on RhoA and RhoC proteins. Stress f

SUBMITTER: Nishima S 

PROVIDER: S-EPMC11658116 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature