本文關(guān)鍵詞： 鼻咽癌 Anexelekto TP- 細(xì)胞增殖 細(xì)胞周期　出處：《中國病理生理雜志》2017年08期 　論文類型：期刊論文

【摘要】：目的:探討受體酪氨酸激酶anexelekto(Axl)在鼻咽癌(nasopharyngeal carcinoma,NPC)中的表達(dá)及意義。方法:采用免疫組化法檢測78例NPC和32例鼻咽黏膜慢性炎中Axl的表達(dá),分析Axl蛋白表達(dá)與NPC患者臨床參數(shù)的相關(guān)性。常規(guī)培養(yǎng)NPC細(xì)胞,免疫熒光法檢測不同分化NPC細(xì)胞系CNE1、CNE2Z及C666-1中Axl的蛋白表達(dá)情況。應(yīng)用Axl特異性抑制劑TP-0903處理CNE1和C666-1細(xì)胞,CCK-8實(shí)驗(yàn)檢測細(xì)胞的活力,流式細(xì)胞術(shù)檢測細(xì)胞周期的分布,q PCR檢測Axl和增殖細(xì)胞核抗原(PCNA)的mRNA表達(dá),Western blot檢測Axl及p-Axl蛋白的表達(dá)。結(jié)果:Axl蛋白定位于胞膜和胞質(zhì)。NPC中Axl高表達(dá)陽性率顯著高于鼻咽黏膜慢性炎(P0.01)。Axl高表達(dá)與患者年齡、性別及M分期無關(guān),與臨床分期、T分期和N分期呈正相關(guān)(P0.05)。Axl在高分化CNE1細(xì)胞中低表達(dá),在低分化CNE2Z細(xì)胞和未分化C666-1細(xì)胞中表達(dá)水平明顯增高。TP-0903呈濃度和時(shí)間依賴性抑制NPC細(xì)胞的活性,2 nmol/L TP-0903即具有顯著抑制效應(yīng),能阻滯細(xì)胞周期于G0期,在降低Axl活性的同時(shí)也顯著抑制PCNA的表達(dá)。結(jié)論:Axl高表達(dá)可促進(jìn)NPC的臨床進(jìn)展;TP-0903顯著抑制NPC細(xì)胞的增殖,提示Axl可能在NPC靶向治療中具有一定的價(jià)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.
【作者單位】： 廣東醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院病理生理教研室;廣東醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院病理學(xué)系;廣東醫(yī)科大學(xué)附屬醫(yī)院病理診斷與研究中心;
【基金】：國家自然科學(xué)基金資助項(xiàng)目(No.81402415) 廣東醫(yī)科大學(xué)科研基金(No.Z2013004;No.M2013032) 湛江市科技計(jì)劃項(xiàng)目(No.2013B01077)
【分類號(hào)】：R739.63
【正文快照】： 受體酪氨酸激酶anexelekto(Axl)基因是編碼受體酪氨酸激酶家族基因的成員之一,最初在慢性髓性白血病中被克隆。受體Axl的配體為生長停滯特異性基因6(growth arrest-specific gene 6,GAS6)編碼的GAS6蛋白。Axl/GAS6信號(hào)系統(tǒng)通過活化AKT、細(xì)胞外信號(hào)調(diào)節(jié)激酶(extracellular sign

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