Trichostatin A potentiates TRAIL-induced antitumor effects via inhibition of ERK/FOXM1 pathway in gastric cancer

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Lin LiJia-Fu Ji

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an ideal apoptosis inducer and believed to have promise in cancer therapy, yet part of cancer cells exhibit resistance to TRAIL-mediated apoptosis. This necessitates the exploration of agents that resensitizes cancer cells to TRAIL. In our study, we found that Trichostatin A (TSA), an histone deacetylase (HDAC) inhibitor, augmented TRAIL-induced apoptosis in gastric cancer cells in a caspase-dependent manner. Besides, upregulation of DR5 and downregulation of anti-apoptotic proteins including XIAP, Mcl-1, Bcl-2 and Survivin also contributed to this synergism. Noticeably, TSA treatment inhibited Forkhead boxM1 (FOXM1), which expression level showed negative correlation with TRAIL sensitivity. Similarly, silencing of FOXM1 by small interfering RNA (siRNA) resensitized cancer cells to TRAIL and strengthened the TRAIL-augmenting effect of TSA. In addition, we demonstrated the depletion of FOXM1 was a consequence of the inactivation of ERK mediated by TSA. Collectively, it was first shown that TSA potentiated TRAIL sensitivity via ERK/FOXM1 pathway in gastric cancer cells. FOXM1 might serve as a biomarker for predicting sensitivity to TRAIL.

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Citations

Sep 11, 2016·Progress in Neuro-psychopharmacology & Biological Psychiatry·Xiaoyan QiuYuemin Li
Jul 28, 2016·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Hui ZhangJun Li
Jan 28, 2017·Oncotarget·Filomena AltieriPaolo Arcari
Apr 3, 2021·Molecular Biology Reports·Shruti GuptaKiran Kumar Tejavath

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