Hou Jiyuan,Liu Zimin,Liu Xingan,et al.Knockdown of Erk/Slug signals increases radiosensitivity of MDA-MB-231 cells to γ-rays by upregulating PUMA[J].Chinese Journal of Radiological Medicine and Protection,2014,34(7):484-488 |
Knockdown of Erk/Slug signals increases radiosensitivity of MDA-MB-231 cells to γ-rays by upregulating PUMA |
Received:November 17, 2013 |
DOI:10.3760/cma.j.issn.0254-5098.2014.07.002 |
KeyWords:Radiotherapy Breast carcinoma Slug ERK1/2 PUMA |
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Abstract:: |
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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