Target and resistance-related proteins of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand on myeloma cell lines.
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.
Department of Hematology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Yuan
Y
Jian
Ministry of Education Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China.
Yuling
Y
Chen
Department of Hematology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Chuanying
C
Geng
Department of Hematology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Nian
N
Liu
Department of Hematology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Guangzhong
G
Yang
Department of Hematology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Jinwei
J
Liu
Department of Hematology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Xin
X
Li
Ministry of Education Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China.
Haiteng
H
Deng
Department of Hematology, Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
Wenming
W
Chen
multiple myeloma; proteomics; recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand; resistant-related protein; target protein