抄録
Purpose: Radiation therapy is an important cancer modality, especially in the treatment of lung cancer. However, recent studies have shown that radiation can actually increase invasion by several cancer types, including glioma, breast cancer, melanoma, pancreatic cancer and hepatocellular carcinoma. The purpose of this study was to investigate the effect of radiation on the invasion of the pulmonary adenocarcinoma cell line, A549.
Methods and Materials: Invasion of A549 cells irradiated with 2 Gy and 4 Gy doses of γ-ray was detected using transwell matrigel invasion assay. The level of matrix metalloproteinase (MMP) 2 and phosphorylated STAT3 was detected by reverse transcription PCR and/or immunoblotting. The enzyme activity of MMP-2 was examined by gelatin zymography.
Results: The invasiveness of A549 cells was significantly enhanced by γ-ray radiation at dose levels of either 2 Gy or 4 Gy. Furthermore, radiation was found to promote the transcription and expression of MMP-2, and increase MMP-2 enzyme activity. Radiation activated the phosphorylation of STAT3 and promoted the nucleic localization of STAT3. Blocking STAT3 phosphorylation using a special inhibitor (AG490) suppressed the radiation-induced elevation of MMP-2 expression, enzyme activity and invasiveness of A549 cells. Finally, we also found that expression of vascular endothelial growth factor (VEGF) could be up-regulated by radiation, which was also associated with the activation of STAT3.
Conclusions: Our results indicated that radiation resulted in the activation of STAT3, which subsequently entered the nucleus and triggered the transcription of VEGF and MMP-2. This in turn led to the increased invasiveness of A549 cells.
