Target and resistance-related proteins of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand on myeloma cell lines
Target and resistance-related proteins of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand on myeloma cell lines
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DOI：
10.3892/br.2016.650
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发表时间：
2016-06-01
影响因子：
2.3
通讯作者：
Chen, Wenming
中科院分区：
文献类型：
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作者：
Jian, Yuan;Chen, Yuling;Chen, Wenming
重组突变型人肿瘤坏死因子相关凋亡诱导配体（rmhTRAIL）已成为治疗多发性骨髓瘤（MM）的潜在药物。然而，rmhTRAIL对MM细胞的确切靶点和耐药机制仍有待阐明。本研究旨在研究rmhTRAIL对骨髓瘤细胞系的靶向作用及耐药相关蛋白。选择TRAIL敏感的骨髓瘤细胞系RPMI 8226和TRAIL耐药的骨髓瘤细胞系U266，通过液相色谱-串联质谱法分析两种细胞系之间在rmhTRAIL施用之前和之后的差异表达蛋白。结果显示，TRAIL处理后，6种骨化相关蛋白，即钙蛋白酶小亚基1（CPNS 1）、peflin（PEF 1）、B细胞受体相关蛋白31（BAP 31）、骨化相关斑点样蛋白CARD（ASC）、BAG家族分子伴侣调节因子2（BAG 2）和染色体盒蛋白同源物3（CBX 3），在RPMI 8226细胞中上调，而在U266细胞中没有发现变化。此外，与rmhTRAIL处理之前和之后的RPMI-8226细胞相比，小泛素相关修饰物1和几种其他泛素蛋白酶体途径（UPP）相关蛋白在TRAIL抗性细胞U266中表达更高水平。这些结果提示CPNS 1、PEF 1、BAP 31、ASC、BAG 2和CBX 3可能是rmhTRAIL作用于RPMI 8226细胞的靶蛋白，而UPP可能在介导U266细胞对TRAIL的耐药性中起重要作用。
Recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) has become a potential therapeutic drug for multiple myelomay(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.