title: Radiation enhances the invasion abilities of pulmonary adenocarcinoma cells via STAT3.
abstract: In the present study, the effect of radiation on the invasion of the pulmonary adenocarcinoma cell line, A549, was investigated. Invasion of A549 cells irradiated with 2 and 4 Gy doses of γ‑ray was detected using the transwell Matrigel invasion assay. Levels of matrix metalloproteinase 2 (MMP‑2) and phosphorylated signal transducer and activator of transcription 3 (STAT3) were detected by reverse transcription PCR (RT-PCR) and/or immunoblotting. The enzyme activity of MMP‑2 was examined by gelatin zymography. Results demonstrated that the invasion of A549 cells was significantly enhanced by γ‑ray radiation at doses of 2 or 4 Gy. In addition, exposure to radiation was found to promote transcriptional expression of MMP‑2 and increase MMP‑2 enzyme activity. Irradiation activated the phosphorylation of STAT3 and promoted the nuclear localization of STAT3. The blockage of STAT3 phosphorylation using a specific inhibitor (AG490) suppressed the irradiation‑induced elevation of MMP‑2 expression, enzyme activity and invasion of A549 cells. Finally, the expression of vascular endothelial growth factor (VEGF) was found to be upregulated by radiation, which was associated with the activation of STAT3. Results of the current study indicate that irradiation leads to activation of STAT3 and translocation to the nucleus, leading to activation of VEGF and MMP‑2 transcription, resulting in the increased invasion of A549 cells.
authors.affiliation: Department of Experimental Therapy of ARS, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: Fengsheng
authors.initials: F
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Jiang
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Dong
authors.forename: Tao
authors.initials: T
authors.lastname: Yan
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; D020032:Tyrphostins; D042461:Vascular Endothelial Growth Factor A; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D020778:Matrix Metalloproteinase 2