Knockdown of Erk/Slug signals increases radiosensitivity of MDA-MB-231 cells to γ-rays by upregulating PUMA
Hou Jiyuan, Liu Xingan, Shan Guoyong
Published 2014-07-25
Cite as Chin J Radiol Med Prot, 2014,34(07): 484-488. DOI: 10.3760/cma.j.issn.0254-5098.2014.07.002
Abstract
Objective To study the role Erk/Slug signal pathway in the radiosensitivity of MDAMB-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-231cells 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.
Key words:
Radiotherapy; Breast carcinoma; Slug; ERK1/2; PUMA
Contributor Information
Hou Jiyuan
Department of Radiotherapy, Zhengzhou People's Hospital, Zhengzhou 450000, China
Liu Xingan
Department of Radiotherapy, Zhengzhou People's Hospital, Zhengzhou 450000, China
Shan Guoyong
Department of Radiotherapy, Zhengzhou People's Hospital, Zhengzhou 450000, China