Enhanced radiosensitivity of SW480 cells via TRAIL up-regulation mediated by Egr-1 promoter.
Radiosensitization of cancer cells to irradiation could improve the efficacy of radiotherapy. The early transcriptional factor (Egr-1) promoter induced expression of downstream genes after irradiation. TNF-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in malignant cells, but displayed little or no toxicity on normal cells. In this study, we constructed pcDNA3.1-Egr-1-TRAIL (pEgr.1-TRAIL) recombinant plasmid and evaluated its effect on human colon cancer cell line SW480. pEgr.1-TRAIL transfection combined with radiotherapy caused dramatically elevation of TRAIL expression both in mRNA and protein levels, much lower radiobiological parameters in clonogenic assays, accompanied by remarkably increase in apoptosis ratio. Furthermore, pEgr.1-TRAIL transfected cells displayed higher proportion in G0/G1 phase. Our results suggested that pEgr.1-TRAIL can sensitize SW480 cells to radiation, and the radiosensitization is related to cell cycle changes and apoptosis mediated by up-regulation of TRAIL expression. These findings support the potential future application of genetic radiotherapy against carcinoma.
Hu
Y
Y
Department of Radiation and Medical Oncology, Wuhan University, Wuhan, 430071, P.R. China.
Ouyang
W
W
Wu
F
F
Cao
C H
CH
Wang
K
K
Liao
Z K
ZK
Zhong
Y H
YH
Zhou
F X
FX
Liu
S Q
SQ
Xia
L
L
Zhou
Y F
YF
Xie
C H
CH
D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011836:Radiation Tolerance / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human