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外源性硫化氢通过激活Akt信号通路对多发性骨髓瘤细胞发挥增殖、抗凋亡、迁移作用并加速细胞周期进程。

Exogenous hydrogen sulfide exerts proliferation, anti-apoptosis, migration effects and accelerates cell cycle progression in multiple myeloma cells via activating the Akt pathway.

作者信息

Zheng Dong, Chen Ziang, Chen Jingfu, Zhuang Xiaomin, Feng Jianqiang, Li Juan

机构信息

Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.

Department of Cardiovasology and Cardiac Care Unit (CCU), Huangpu Division, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.

出版信息

Oncol Rep. 2016 Oct;36(4):1909-16. doi: 10.3892/or.2016.5014. Epub 2016 Aug 11.

Abstract

Hydrogen sulfide (H2S), regarded as the third gaseous transmitter, mediates and induces various biological effects. The present study investigated the effects of H2S on multiple myeloma cell progression via amplifying the activation of Akt pathway in multiple myeloma cells. The level of H2S produced in multiple myeloma (MM) patients and healthy subjects was measured using enzyme-linked immunosorbent assay (ELISA). MM cells were treated with 500 µmol/l NaHS (a donor of H2S) for 24 h. The expression levels of phosphorylated-Akt (p-Akt), Bcl-2 and caspase-3 were measured by western blot assay. Cell viability was detected by Cell Counting Kit 8 (CCK-8). The cell cycle was analyzed by flow cytometry. Our results show that the concentration of H2S was higher in MM patients and that it increased in parallel with disease progression. Treating MM cells with 500 µmol/l NaHS for 24 h markedly increased the expression level of Bcl-2 and the activation of p-Akt, however, the expression level of caspase-3 was decreased, cell viability was increased, and cell cycle progression was accelerated in MM cells. NaHS also induced migration in MM cells in transwell migration assay. Furthermore, co-treatment of MM cells with 500 µmol/l NaHS and 50 µmol/l LY294002 for 24 h significantly overset these effects. In conclusion, our findings demonstrate that the Akt pathway contributes to NaHS-induced cell proliferation, migration and acceleration of cell cycle progression in MM cells.

摘要

硫化氢(H₂S)被视为第三种气体递质,介导并诱发多种生物学效应。本研究通过增强多发性骨髓瘤细胞中Akt信号通路的激活,探讨了H₂S对多发性骨髓瘤细胞进展的影响。采用酶联免疫吸附测定法(ELISA)检测多发性骨髓瘤(MM)患者和健康受试者体内产生的H₂S水平。用500 μmol/l NaHS(一种H₂S供体)处理MM细胞24小时。通过蛋白质免疫印迹法检测磷酸化Akt(p-Akt)、Bcl-2和caspase-3的表达水平。使用细胞计数试剂盒8(CCK-8)检测细胞活力。通过流式细胞术分析细胞周期。我们的结果表明,MM患者体内H₂S浓度较高,且其浓度随疾病进展而升高。用500 μmol/l NaHS处理MM细胞24小时后,Bcl-2的表达水平和p-Akt的激活显著增加,然而,caspase-3的表达水平降低,细胞活力增加,MM细胞的细胞周期进程加快。在transwell迁移试验中,NaHS还诱导MM细胞迁移。此外,将MM细胞与500 μmol/l NaHS和50 μmol/l LY294002共同处理24小时可显著抵消这些效应。总之,我们的研究结果表明,Akt信号通路促进了NaHS诱导的MM细胞增殖、迁移和细胞周期进程加速。

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