γ射线照射对肺腺癌细胞迁移能力的影响及其分子机制

Effect of γ-ray irradiation on migration of pulmonary adenocarcinoma cells and its mechanism

目的探讨辐射对肺腺癌A549细胞迁移能力的影响及其所依赖的信号通路。方法划痕实验检测2和4 Gyγ射线照射后A549细胞的迁移能力,Western印迹实验检测STAT3及磷酸化STAT3水平,ELISA法检测IL-6的分泌水平,间接免疫荧光染色观察STAT3在细胞内定位情况。结果 2或4 Gyγ射线照射均能显著增强A549细胞的迁移能力,并能激活STAT3的磷酸化,促进STAT3入核以及IL-6的分泌。JAK-2激酶特异性抑制剂AG490能阻断辐射诱导的STAT3磷酸化并进一步抑制辐射诱导的A549细胞迁移。结论本研究结果表明辐射能通过激活JAK-2/STAT3信号通路促进A549细胞的迁移,而IL-6可能参与了辐射诱导的JAK-2/STAT3信号通路的激活。

Objective To investigate the effect of radiation on the migration of the pulmonary adenocarcinoma cell line,A549,and the mechanism involved in this process.Methods Migration of A549 cells irradiated with 2 and 4 Gy doses of γ-ray was detected using wound healing assay.The level of STAT3 and phosphorylated STAT3 was detected by Western blot.The distribution of p-STAT3（Y705） in A549 cells was examined by immunofluorescence staining.Finally,the secretion of IL-6 by cultured A549 cells was detected by ELISA.Results The migration of A549 cells was significantly enhanced by γ-ray radiation at dose levels of either 2 or 4 Gy.Furthermore,radiation was found to activate the phosphorylation of STAT3 and promote the nucleus localization of STAT3.The result of ELISA showed that the secretion of IL-6 increased after 2 or 4 Gy doses of γ-ray.AG490,a special inhibitor of JAK-2,suppressed the radiation-induced phosphorylation of STAT3 and migration of A549 cells.Conclusion Our results indicated that radiation results in the activation of JAK-2/STAT3 pathway,which triggers the migration of A549 cells.It is possible that the IL-6 is involved in the radiation-induced activation of JAK-2/STAT3 pathway.