Role of VEGF-A/C and CCR-7 in the enhanced metastasis of A549 cells induced by 2 and 4 Gy X-rays in vitroand in vivo

Radiotherapy is a common strategy in treating lung cancer. Accumulating evidence suggested that radiotherapy has the potential to promote the metastasis and invasion of carcinoma cells. In this study, we aimed to testify the role of vascular endothelial growth factor (VEGF) and C-C chemokine receptor-7 (CCR-7) in the metastasis of human adenocarcinoma A549 cells in vivoand in vitro. Nude mice were injected with A549 cells irradiated by 0, 2 and 4 Gy X-rays, respectively. Quantitative detections of VEGF-A/C and CCR-7 mRNA from lung sample were performed by real-time RT-PCR. Small interfering RNA (siRNA) transfection technology was further used to testify the role of the genes in the metastasis of A549 cells. VEGF and CCR-7 mRNA could only be detected 10 weeks post injection in vivowhen visible tumor foci scattered in lung. In addition, VEGF-A/C mRNA expressed significantly higher in mice injected with A549 cells irradiated by 2 and 4 X-rays than those with 0 Gy X-rays irradiation. On the other hand, A549 cells with or without X-rays irradiation transfected with VEGF siRAN and CCR-7 siRNA showed a dramatic decrease of invasiveness compared to normal A549 cells with or without irradiation. The migration indexes were −0.7, −0.48, −0.34 and −0.32 for A549 cells with CCR-7 siRNA, VEGF siRNA, X-rays combined CCR-7 siRNA and X-rays combined VEGF-siRNA respectively. These results demonstrated that X-rays could promote the metastasis of A549 cells, and VEGF-A/C and CCR-7 mRNA were closely related to the metastasis of A549 cells in vivoand in vitro.