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目的探讨PD 98059通过抑制丝裂原活化蛋白激酶-细胞外信号调节激酶(MRPK-ERK)信号通路是否改变食管癌细胞的放射敏感性。方法用食管癌细胞株EC9706为实验对象,分别接受单纯放射、PD 98059和二者结合处理。通过Western印记法证实PD 98059可下调ERK活性。采用成克隆法定量分析细胞增殖性死亡。通过流式细胞仪检测细胞凋亡情况。结果单纯PD 98059(10μmol/L)可抑制ERK的磷酸化,而单纯放射对ERK的活性无明显影响,二者结合可提高对ERK活性的抑制作用。PD 98059(10μmol/L)在放射前与细胞作用1h及放射后作用10d均可提高EC9706细胞对放射的敏感性。PD 98059结合放射可增加EC9706细胞增殖性死亡,D0值的放射增敏比为1.69。PD 98059可增加EC9706细胞放射后诱导的细胞凋亡。结论PD 98059通过抑制MAPK降低ERK活性,增加EC9706细胞对放射的敏感性,为筛选放射敏感剂临床实验提供了依据。
Objective To investigate whether PD 98059 can alter the radiosensitivity of esophageal cancer cells by inhibiting the mitogen-activated protein kinase extracellular signal-regulated kinase (MRPK-ERK) signaling pathway. Methods The esophageal cancer cell line EC9706 was used as the experimental subject and received radio-exposure alone, PD 98059 and the combination of the two. Western blotting confirmed that PD 98059 downregulated ERK activity. Quantitative analysis of cell proliferative death using cloning method. Apoptosis was detected by flow cytometry. Results PD 98059 alone (10μmol / L) inhibited the phosphorylation of ERK. However, radiotherapy alone had no effect on the activity of ERK. The combination of both could increase the inhibitory effect on ERK activity. The sensitivity of EC9706 cells to radiation was enhanced by PD 98059 (10 μmol / L) for 1 h before irradiation and 1 h after irradiation. PD 98059 combined with radiation increased the proliferative death of EC9706 cells, with a radiocontrast ratio of 1.69 for the D0 value. PD 98059 increases the apoptosis induced by radiation in EC9706 cells. Conclusion PD 98059 can reduce the ERK activity by inhibiting MAPK and increase the sensitivity of EC9706 cells to radiation, which provides a basis for screening clinical trials of radiosensitizers.