X线电离辐射通过上调c-Myc表达促进肺癌A549细胞上皮间质转化

X-ray ionizing radiation up-regulates c-Myc expression and promotes epithelial-mesenchymal transition in lung cancer cell line A549

目的:探讨电离辐射对肺癌A549细胞上皮间质转化(EMT)的影响及其可能机制。方法:采用不同剂量(0 Gy、1 Gy、2 Gy、4 Gy和8 Gy)的X射线分别照射肺癌A549细胞不同时间,通过倒置显微镜观察X射线照射12 h、24 h和48 h时肺癌A549细胞形态的改变;Western blot检测X射线照射12 h与24 h时EMT相关蛋白vimentin、N-cadherin及E-cadherin和转录因子c-Myc的表达。结果:照射后肺癌A549细胞轮廓不清,突起增多,边缘不规则且呈煎蛋样塌陷,以8 Gy X射线照射48 h时肺癌A549细胞上皮间质化形态最明显。与0 Gy照射剂量对照组相比,vimentin虽然于4 Gy剂量照射12 h时下调,但是处理24 h时各剂量照射组vimentin均表现为上调,其中2 Gy剂量照射组其上调最明显(P<0.01);与0 Gy照射剂量对照组相比,1 Gy、2 Gy及4 Gy照射组照射肺癌A549细胞24 h后其N-cadherin表达上调(P<0.05);各照射剂量对肺癌A549细胞E-cadherin表达没有显著影响。照射24 h后肺癌A549细胞c-Myc表达上调,以4 Gy剂量照射组表达差异最明显(P<0.01)。结论:X线电离辐射可能通过上调c-Myc表达促进肺癌A549细胞发生上皮间质转化。

AIM：To investigate the effect of ionizing radiation on epithelial-mesenchymal transition in lung cancer cell line A549 and its possible mechanism.METHODS： The lung cancer A549 cells were irradiated with different doses （0 Gy, 1 Gy, 2 Gy, 4 Gy and 8 Gy） of X-ray for different time. The morphological changes of the cells were observed under inverted microscope at time points of 12 h, 24 h and 48 h. The expression of vimentin, N-cadherin, E-cadherin and transcription factor c-Myc was detected by Western blot at the time points of 12 h and 24 h.RESULTS： After ionizing radiation, the contours of the A549 cells were unclear, the protrusions increased, and the edges were irregular, with fried egg-like collapses. The mesenchymal morphology of the A549 cells was most obvious after irradiation at 8 Gy for 48 h. Compared with 0 Gy irradiation group, the expression of vimentin was down-regulated seemingly 12 h after irradiation, but up-regulated in 2 Gy, 4 Gy and 8 Gy irradiation groups for 24 h, and the most obvious effect was observed in 2 Gy irradiation group （P〈0.01）. Compared with 0 Gy irradiation group, the expression of N-cadherin was up-regulated in 1 Gy, 2 Gy and 4 Gy irradiation groups for 24 h （P〈0.05）, while the expression of E-cadherin was not influenced. The up-regulation of vimentin expression in lung cancer cell line A549 was positively correlated with c-Myc expression.CONCLUSION： Ionizing radiation may promotes epithelial-mesenchymal transition in the lung cancer cell line A549 by up-regulating the c-Myc expression.