The IAP antagonist birinapant potentiates bortezomib anti-myeloma activity in vitro and in vivo.

ABSTRACT:

Background

Mechanisms by which Smac mimetics (SMs) interact with proteasome inhibitors (e.g., bortezomib) are largely unknown, particularly in multiple myeloma (MM), a disease in which bortezomib represents a mainstay of therapy.

Methods

Interactions between the clinically relevant IAP (inhibitor of apoptosis protein) antagonist birinapant (TL32711) and the proteasome inhibitor bortezomib were investigated in multiple myeloma (MM) cell lines and primary cells, as well as in vivo models. Induction of apoptosis and changes in gene and protein expression were monitored using MM cell lines and confirmed in primary MM cell populations. Genetically modified cells (e.g., exhibiting shRNA knockdown or ectopic expression) were employed to evaluate the functional significance of birin

SUBMITTER: Zhou L 

PROVIDER: S-EPMC6407248 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature