受体酪氨酸激酶Axl高表达促进鼻咽癌临床进展

发布时间：2018-01-22 09:10

本文关键词： 鼻咽癌 Anexelekto TP- 细胞增殖细胞周期　出处：《中国病理生理杂志》2017年08期 　论文类型：期刊论文

【摘要】：目的:探讨受体酪氨酸激酶anexelekto(Axl)在鼻咽癌(nasopharyngeal carcinoma,NPC)中的表达及意义。方法:采用免疫组化法检测78例NPC和32例鼻咽黏膜慢性炎中Axl的表达,分析Axl蛋白表达与NPC患者临床参数的相关性。常规培养NPC细胞,免疫荧光法检测不同分化NPC细胞系CNE1、CNE2Z及C666-1中Axl的蛋白表达情况。应用Axl特异性抑制剂TP-0903处理CNE1和C666-1细胞,CCK-8实验检测细胞的活力,流式细胞术检测细胞周期的分布,q PCR检测Axl和增殖细胞核抗原(PCNA)的mRNA表达,Western blot检测Axl及p-Axl蛋白的表达。结果:Axl蛋白定位于胞膜和胞质。NPC中Axl高表达阳性率显著高于鼻咽黏膜慢性炎(P0.01)。Axl高表达与患者年龄、性别及M分期无关,与临床分期、T分期和N分期呈正相关(P0.05)。Axl在高分化CNE1细胞中低表达,在低分化CNE2Z细胞和未分化C666-1细胞中表达水平明显增高。TP-0903呈浓度和时间依赖性抑制NPC细胞的活性,2 nmol/L TP-0903即具有显著抑制效应,能阻滞细胞周期于G0期,在降低Axl活性的同时也显著抑制PCNA的表达。结论:Axl高表达可促进NPC的临床进展;TP-0903显著抑制NPC细胞的增殖,提示Axl可能在NPC靶向治疗中具有一定的价值。
[Abstract]:Objective: to investigate the role of receptor tyrosine kinase anexelek to axl in nasopharyngeal carcinoma (NPC) nasopharyngeal carcinoma. Methods: immunohistochemical method was used to detect the expression of Axl in 78 cases of NPC and 32 cases of chronic nasopharyngeal mucositis. To analyze the correlation between the expression of Axl protein and the clinical parameters of patients with NPC, NPC cells were cultured routinely, and different differentiated NPC cell lines CNE1 were detected by immunofluorescence. The expression of Axl protein in CNE2Z and C666-1 cells was studied. CNE1 and C666-1 cells were treated with TP-0903, a specific inhibitor of Axl. Cell viability was detected by CCK-8 assay, cell cycle distribution was detected by flow cytometry and mRNA expression of Axl and proliferating cell nuclear antigen (PCNA) were detected by Axl and proliferating cell nuclear antigen (PCNA). Western blot was used to detect the expression of Axl and p-Axl protein. The positive rate of Axl overexpression in membrane and cytoplasm of Axl protein was significantly higher than that in chronic nasopharyngeal mucositis (P < 0.05). The high expression of P0.01n.Axl was associated with the age of the patients. Gender and M stage were not related to T stage and N stage. There was a positive correlation between P0.05 and axl expression in well-differentiated CNE1 cells. The expression level in poorly differentiated CNE2Z cells and undifferentiated C666-1 cells was significantly increased. TP-0903 inhibited the activity of NPC cells in a concentration-and time-dependent manner. 2 nmol/L TP-0903 had obvious inhibitory effect and could block cell cycle in G0 phase. Conclusion the high expression of Axl can promote the clinical progress of NPC. TP-0903 significantly inhibited the proliferation of NPC cells, suggesting that Axl may be valuable in NPC targeted therapy.
【作者单位】：广东医科大学基础医学院病理生理教研室;广东医科大学基础医学院病理学系;广东医科大学附属医院病理诊断与研究中心;
【基金】：国家自然科学基金资助项目(No.81402415) 广东医科大学科研基金(No.Z2013004;No.M2013032) 湛江市科技计划项目(No.2013B01077)
【分类号】：R739.63
【正文快照】： 受体酪氨酸激酶anexelekto(Axl)基因是编码受体酪氨酸激酶家族基因的成员之一,最初在慢性髓性白血病中被克隆。受体Axl的配体为生长停滞特异性基因6(growth arrest-specific gene 6,GAS6)编码的GAS6蛋白。Axl/GAS6信号系统通过活化AKT、细胞外信号调节激酶(extracellular sign

【相似文献】