Panbinostat decreases cFLIP and enhances killing of cancer cells by immunotoxin LMB-100 by stimulating the extrinsic apoptotic pathway.

ABSTRACT: LMB-100 (RG7787) is a recombinant immunotoxin, which kills mesothelin-expressing cancer cells and now being evaluated in phase 1 trials. To enhance the anti-tumor activity of LMB-100, we have searched for agents, already approved for cancer therapy, that can be combined with LMB-100 to increase its efficacy. Panbinostat is a pan-histone deacetylase inhibitor that is used to treat multiple myeloma. We incubated different types of cancer cells with panbinostat and LMB-100 and found that they interacted synergistically to cause cell death. We found that panbinostat and the combination increased levels of mRNAs encoding TNF/TNFR family members, as well as BNIP3L and CASP-9, and markedly decreased mRNA levels for c-FLIP and BID. Western blots confirmed a fall in leve

SUBMITTER: Liu XF 

PROVIDER: S-EPMC5675634 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature