| 侯继院,刘自民,刘兴安,单国用,曹伟红.靶向Erk/Slug信号上调PUMA表达增强乳腺癌MDA-MB-231细胞对γ射线的敏感性[J].中华放射医学与防护杂志,2014,34(7):484-488 |
| 靶向Erk/Slug信号上调PUMA表达增强乳腺癌MDA-MB-231细胞对γ射线的敏感性 |
| Knockdown of Erk/Slug signals increases radiosensitivity of MDA-MB-231 cells to γ-rays by upregulating PUMA |
| 投稿时间：2013-11-17 |
| DOI：10.3760/cma.j.issn.0254-5098.2014.07.002 |
| 中文关键词: 乳腺癌 放疗 Slug ERK1/2 PUMA |
| 英文关键词:Radiotherapy Breast carcinoma Slug ERK1/2 PUMA |
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| 中文摘要: |
| 目的 研究Erk/Slug信号通路在乳腺癌细胞MDA-MB-231放射敏感性中的作用。方法 通过以NF-κB p65 siRNA、PUMA siRNA或Slug siRNA转染MDA-MB-231细胞，或以U0126处理该细胞之后，以4 Gy γ射线进行照射，在照射后的不同时间点检测细胞内Erk1/2、NF-κB p65、Slug和PUMA蛋白的表达，以MTT比色法检测细胞存活率，以TUNEL法检测细胞凋亡。 结果 与单纯照射组相比，NF-κB p65 siRNA/4 Gy 组，细胞PUMA表达明显下降；U0126/4 Gy组，细胞Erk1/2和Slug蛋白表达明显降低，PUMA表达明显升高；Slug siRNA/4 Gy组，Erk1/2蛋白表达无变化，但PUMA蛋白表达明显增加；同时，U0126/4 Gy组和Slug siRNA/4 Gy组，细胞照射48 h后存活率降至最低点，分别为19.78±2.71（F=11.39，P<0.05）和17.41±4.58（F=15.31，P<0.05），细胞凋亡率升至最高点，分别为28.61±4.70（F=9.84，P<0.05）和 27.55±6.41（F=10.31，P<0.05）；NF-κBp65 siRNA/4 Gy组和PUMA siRNA/4 Gy组，细胞照射24h后存活率分别为85.65±9.60（F=12.31，P<0.05）和87.53±11.50（F=13.68，P<0.05），细胞凋亡率明显下降，分别为3.28±0.78（F=10.83，P<0.05）和3.46±0.84（F=9.92，P<0.05）。结论 γ 射线照射后24 h内，MDA-MB-231细胞敏感性与依赖于NF-κB上调的PUMA表达有关；而照射24 h后，细胞的辐射抵抗性与依赖于Erk1/2上调的Slug表达有关，后者对PUMA表达有明显的抑制作用。 |
| 英文摘要: |
| Objective To study the role Erk/Slug signal pathway in the radiosensitivity of MDA-MB-231 cells.Methods MDA-MB-231 cells were transfected with NF-κBp65 siRNA,PUMA siRNA and Slug siRNA respectively or treated with U0126 for 24h, then the cells were irradiated with 4 Gy γ-ray. At different time points post-irradiation, the expressions of Erk1/2, NF-κBp65, Slug and PUMA protein were detected. The cell survival rate and apoptotic index were detected by MTT and TUNEL methods.Resluts Compared with 4 Gy irradiated group, the expression of PUMA was reduced in NF-κB p65 siRNA/4 Gy group, the expressions of Slug and Erk1/2 were obviously decreased but PUMA increased in U0126/4 Gy group, the expression of Erk1/2 had no change but the expression of PUMA increased significantly in Slug siRNA/4 Gyγ group. Meanwhile, at 48h post-irradiation, for U0126/4 Gy group and Slug siRNA/4 Gy group, cells survival rates were decreased to 19.78±2.71 (F=11.39, P<0.05) and 17.41±4.58 (F=15.31, P<0.05), cell apoptosis rates were 28.61±4.70 (F=9.84, P<0.05) and 27.55±6.41 (F=10.31,,P<0.05), respectively. At 24 h post-irradiation, for NF-κB p65 siRNA/4 Gy group and PUMA siRNA/4 Gy group, cell survival rates approached to 85.65±9.60 (F=12.31, P<0.05) and 87.53±11.50 (F=13.68, P<0.05), and cell apoptosis rates declined to 3.28±0.78 (F=10.83, P<0.05) and 3.46±0.84 (F=9.92, P<0.05). Conclusions The radiosensitivity of MDA-MB-231 cells was relative to the induction of NF-κB up-regulated PUMA, and the radioresistance was caused by the up-regulation of Slug induced by Erk1/2, which inhibited the expression of PUMA. |
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