Target and resistance-related proteins of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand on myeloma cell lines

Abstract

Abstract. Recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) has become a potential therapeutic drug for multiple myeloma (MM). However, the exact targets and resistance mechanisms of rmhTRAIL on MM cells remain to be elucidated. The present study aimed to investigate the target and resistance-related proteins of rmhTRAIL on myeloma cell lines. A TRAIL-sensitive myeloma cell line, RPMI 8226, and a TRAIL-resistance one, U266, were chosen and the differentially expressed proteins between the two cell lines were analyzed prior and subsequent to rmhTRAIL administration by a liquid chromatography-tandem mass spectrometry method. The results showed that following TRAIL treatment, 6 apoptosis-related proteins, calpain small subunit 1 (CPNS1), peflin (PEF1), B-cell receptor-associated protein 31 (BAP31), apoptosis-associated speck-like protein containing CARD (ASC), BAG family molecular chaperone regulator 2 (BAG2) and chromobox protein homolog 3 (CBX3), were upregulated in RPMI 8226 cells while no change was identified in the U266 cells. Furthermore, small ubiquitin-related modifier 1 and several other ubiquitin proteasome pathway (UPP)-related proteins expressed higher levels in TRAIL-resistant cells U266 compared to the RPMI-8226 cells prior and subsequent to rmhTRAIL treatment. These results suggested that CPNS1, PEF1, BAP31, ASC, BAG2 and CBX3 were possibly target proteins of rmhTRAIL on RPMI 8226 cells, while UPP may have a vital role in mediating TRAIL-resistance in U266 cells.

Fucoxanthin and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Synergistically Promotes Apoptosis of Human Cervical Cancer Cells by Targeting PI3K/Akt/NF-κB Signaling Pathway

“…TRAIL has become a potential therapeutic drug for cancers, but effects are different between TRAIL-sensitive cancer cells and TRAIL-resistant cancer cells. TRAIL was sensitive to various types of cancer cells, including prostate and bladder cancer cells [ 20 ] and myeloma cell line RPMI 8226 [ 21 ], and significantly decreased cell proliferation rate in these cancer cells. Moreover, not all cancer cells are susceptible to TRAIL-mediated cell apoptosis.…”

SAHA-induced TRAIL-sensitisation of Multiple Myeloma cells is enhanced in 3D cell culture

“…Apoptosis-Inducing Ligand (TRAIL) and agonistic Death Receptor antibodies have been completed in several tumour types [7][8][9] including MM [10]. Unfortunately, TRAIL resistance develops in vitro [11] and in clinical trials, TRAIL insensitivity may be present in most tumours [12]. Consequently combined therapy of TRAIL with other anti-tumour agents is required to restore the TRAIL sensitivity [9].…”

Synergistic effects of rmhTRAIL and 17-AAG on the proliferation and apoptosis of multiple myeloma cells

“…TRAIL can induce apoptosis of tumor cells without damaging normal cells. As the application of wild-type TRAIL has limited stability and biological activity, recombinant mutant human TRAIL (rmhTRAIL) has been developed [4]. It has been reported that rmhTRAIL can remarkably inhibit the proliferation of tumor cell lines from the lung, colon, and breast cancer [5].…”

“…It has been reported that rmhTRAIL can remarkably inhibit the proliferation of tumor cell lines from the lung, colon, and breast cancer [5]. Because rmhTRAIL can selectively induce apoptosis in various types of tumor cells, including myeloma cells, it is a potential therapeutic drug for MM [4]. However, as some tumor cells from the breast, colon, and bone marrow are not sensitive to rmhTRAIL, the clinical application of rmhTRAIL is significantly limited [4,6].…”