Astragalus Polysaccharide Inhibits Ionizing Radiation-Induced Bystander Effects by Regulating MAPK/NF-kB Signaling Pathway in Bone Mesenchymal Stem Cells (BMSCs).
Astragalus Polysaccharide Inhibits Ionizing Radiation-Induced Bystander Effects by Regulating MAPK/NF-kB Signaling Pathway in Bone Mesenchymal Stem Cells (BMSCs).
复制标题
黄芪多糖通过调节骨间充质干细胞 (BMSC) 中的 MAPK/NF-kB 信号通路来抑制电离辐射引起的旁观者效应。
DOI：
10.12659/msm.909153
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发表时间：
2018-07-06
期刊：
影响因子：
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通讯作者：
Liu Y
中科院分区：
文献类型：
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作者：
Zhang L;Luo Y;Lu Z;He J;Wang L;Zhang L;Zhang Y;Liu Y
本研究探讨了黄芪多糖（APS）对受照射的A549细胞诱导的人骨髓间充质干细胞（BMSCs）辐射旁效应（RIBE）的影响。
用2 Gy的X射线照射A549细胞以获得条件培养基。将BMSCs与条件培养基或APS一起培养。通过酶联免疫吸附测定（ELISA）检测活性氧（ROS）和转化生长因子 -β（TGF -β）的水平。分别通过CCK - 8法、集落形成实验、微核试验和免疫荧光法检测细胞存活、基因组不稳定性和DNA损伤。通过蛋白质印迹法检测旁效应细胞中p38、c - Jun N - 末端激酶（JNK）、细胞外调节蛋白激酶（ERK1/2）、P65和环氧合酶 - 2（COX - 2）的蛋白及磷酸化蛋白表达。
用条件培养基刺激后，COX - 2和ROS的表达增加；预先将细胞暴露于APS可抑制这种效应。用条件培养基刺激后，BMSCs的生长和集落形成率降低；预先将细胞暴露于APS可抑制这种效应。此外，用条件培养基处理后，微核率和53BP1焦点数量增加；APS可抑制BMSCs中这种增加。条件培养基使磷酸化的p38、JNK、ERK1/2、NF - κB P65和COX - 2蛋白水平升高，但预先用APS处理可使其降低。
受照射的A549细胞诱导的BMSCs中的RIBE是由条件培养基中的ROS介导的，并且可能与BMSCs中的丝裂原活化蛋白激酶（MAPK）/核因子 - κB（NF - κB）信号通路有关。APS可能通过调节MAPK/NF - κB通路阻断RIBE。
This study investigated the effect of Astragalus polysaccharides (APS) on radiation-induced bystander effects (RIBE) in human bone mesenchymal stem cells (BMSCs) induced by irradiated A549 cells. A549 cells were irradiated with 2 Gy X-rays to obtain conditioned medium. BMSCs were incubated with the conditioned medium or APS. The levels of reactive oxygen species (ROS) and TGF-β were detected by ELISA. Cell survival, genomic instability, and DNA damages were detected by CCK-8 assay, colony formation assay, the micronucleus test and immunofluorescence assay, respectively. The protein and phosphorylation protein expression of p38, c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK1/2), P65, and cyclooxygenase-2 (COX-2) in bystander effect cells were detected by Western blot. The expression of COX-2 and ROS increased following stimulation with conditioned medium; this effect was inhibited by pre-exposing the cells to APS. BMSCs growth and colony formation rate decreased following stimulation with conditioned medium; this effect was suppressed by pre-exposing the cells to APS. In addition, the micronucleus rate and 53BP1 foci number increased after treatment with conditioned medium; this increase in BMSCs was inhibited by APS. The levels of phosphorylated p38, JNK, ERK1/2, NF-κB P65, and COX-2 proteins were increased by conditioned medium but were decreased by pre-treatment with APS. RIBE in BMSCs induced by the irradiated A549 was mediated by the ROS in the conditioned medium and might be related to MAPK/NF-κB signal pathways in BMSCs. APS may block RIBE through regulating the MAPK/NF-κB pathway.