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目的:研究肿瘤血管导向性干扰素IFN-α2a-NGR抗肿瘤效应的分子机制,发现影响干扰素敏感性的关键信号分子,提高耐药肿瘤细胞敏感性。方法:培养IFNAR高表达细胞株A549、IFNAR低表达细胞株MKN-45,通过MTT检测IFN-α2a-NGR的抗细胞增殖活性,流式细胞术(FCM)、Western blot检测IFN-α2a-NGR处理前后STAT1、p-STAT1、p53、OAS与SOCS1的表达变化,合成siRNA靶向干涉SOCS1。结果:IFN-α2a-NGR刺激后,A549中,p-STAT1、p53、OAS与SOCS1表达上调;MKN-45中P53、OAS无显著变化,SOCS1显著上调。靶向干涉SOCS1后,MKN-45对IFN-α2a-NGR的敏感性增加[抑制率从(14.69±1.05)%提高到(36.97±2.05)%]。结论:IFN-α2a-NGR与IFN-α2a在细胞和分子水平的效应基本一致,p-STAT1、p53与SOCS1可影响细胞对干扰素的敏感性,通过siRNA沉默技术可提高耐药细胞株敏感性,为IFN-α2a-NGR的进一步研发奠定了基础。
Objective: To study the molecular mechanism of anti-tumor effect of tumor-targeting interferon-α2a-NGR and to find the key signaling molecules that affect the sensitivity of interferon and to improve the sensitivity of drug-resistant tumor cells. Methods: IFN-α2a-NGR and IFN-α2a-NGR were transfected into A549 cells and IFN-α2a-NGR cells by flow cytometry (FCM) and Western blot respectively. Before and after STAT1, p-STAT1, p53, OAS and SOCS1 expression changes, synthetic siRNA targeted interference SOCS1. Results: After IFN-α2a-NGR stimulation, the expression of p-STAT1, p53, OAS and SOCS1 were up-regulated in A549 cells. There was no significant change in P53 and OAS and SOCS1 in MKN-45 cells. The sensitivity of MKN-45 to IFN-α2a-NGR increased after targeted interference with SOCS1 [inhibition rate increased from (14.69 ± 1.05)% to (36.97 ± 2.05)%]. CONCLUSION: The effect of IFN-α2a-NGR and IFN-α2a at the cellular and molecular level are basically the same. The expression of p-STAT1, p53 and SOCS1 can affect the sensitivity of cells to interferon. SiRNA silencing can increase the susceptibility of drug- , Laid the foundation for the further development of IFN-α2a-NGR.