重组人肿瘤坏死因子相关凋亡诱导配体（rmhTRAIL）与17-烯丙基氨基-17-去甲氧基格尔德霉素（17-AAG）对多发性骨髓瘤细胞增殖和凋亡的协同作用。

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

作者信息

Wang Jing, Li Yun, Sun Wei, Liu Jing, Chen Wenming

机构信息

a Department of hematology , Daqing oil-field general hospital , Daqing City , China.

b Department of infectation , Daqing oil-field general hospital , Daqing City , China.

出版信息

Hematology. 2018 Oct;23(9):620-625. doi: 10.1080/10245332.2018.1449338. Epub 2018 Mar 22.

DOI:10.1080/10245332.2018.1449338

PMID:29566599

Abstract

OBJECTIVE

This study aimed to investigate synergistic effects of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) and heat-shock protein 90 (HSP90) inhibitor (geldanamycin derivative 17 -allylamino- 17-demethoxy -geldanamycin, 17-AAG) on the proliferation and apoptosis of multiple myeloma (MM) cells.

METHODS

MTT assays evaluated inhibitory effects of rmhTRAIL and 17-AAG in different concentrations and treatment durations on the proliferation of RPMI8226 and U266 cells. The half maximal inhibitory concentration was calculated using OriginPro7.5. Synergistic effects of rmhTRAIL and 17-AAG on apoptosis of MM cells were detected using flow cytometry at 24 and 48 h post-treatment. To evaluate synergistic effects of rmhTRAIL and 17-AAG, the Q-value was calculated using King's formula.

RESULTS

rmhTRAIL exhibited significant inhibitory effects on the proliferation of RPMI8226 cells in a dose- and time-dependent manner (>50%), whereas U266 cells were not sensitive to rmhTRAIL (<50%). 17-AAG inhibited the proliferation of RPMI8226 and U266 cells in a dose-dependent manner (>80%). Significant synergistic effects of rmhTRAIL and 17-AAG on the proliferation of RPMI8226 cells were revealed (Q-value > 1.15), whereas synergistic effects were not evident on the proliferation of U266 cells (Q-value < 1.15). rmhTRAIL and 17-AAG exhibited significant synergistic effects on apoptosis of RPMI8226 and U266 cells (Q-value > 1.15).

CONCLUSION

The combined application of rmhTRAIL and 17-AAG revealed favorable synergistic effects in the treatment of MM.

摘要

目的

本研究旨在探讨重组突变型人肿瘤坏死因子相关凋亡诱导配体（rmhTRAIL）与热休克蛋白90（HSP90）抑制剂（格尔德霉素衍生物17-烯丙基氨基-17-去甲氧基-格尔德霉素，17-AAG）对多发性骨髓瘤（MM）细胞增殖和凋亡的协同作用。

方法

MTT法评估不同浓度和处理时间的rmhTRAIL和17-AAG对RPMI8226和U266细胞增殖的抑制作用。使用OriginPro7.5计算半数最大抑制浓度。处理后24小时和48小时，采用流式细胞术检测rmhTRAIL和17-AAG对MM细胞凋亡的协同作用。为评估rmhTRAIL和17-AAG的协同作用，使用金氏公式计算Q值。

结果

rmhTRAIL对RPMI8226细胞的增殖呈剂量和时间依赖性显著抑制作用（>50%），而U266细胞对rmhTRAIL不敏感（<50%）。17-AAG以剂量依赖性方式抑制RPMI8226和U266细胞的增殖（>80%）。rmhTRAIL和17-AAG对RPMI8226细胞的增殖显示出显著的协同作用（Q值>1.15），而对U266细胞的增殖协同作用不明显（Q值<1.15）。rmhTRAIL和17-AAG对RPMI8226和U266细胞的凋亡表现出显著的协同作用（Q值>1.15）。