FOXO3在肺癌组织与肺癌干细胞中的表达特征及其与肺癌分化转移的相关性分析
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摘要
目的分析FOXO3在肺癌组织与肺癌干细胞中的表达特征及其与肺癌分化转移的相关性。方法回顾性分析105例肺癌患者的临床资料,并以35例正常肺组织标本进行对照分析。分别采用免疫组织化学法、Western blot及反转录-聚合酶链反应(RT-PCR)法对肺癌组织和正常肺组织中FOXO3的表达情况进行检测,并用Western blot和RT-PCR法对肺癌干细胞中FOXO3蛋白和mRNA表达水平进行检测,同时比较不同病理类型、分化程度及是否伴有淋巴结转移的肺癌患者FOXO3蛋白表达情况。结果免疫组织化学法检测发现,FOXO3蛋白主要定位于细胞质和细胞间质中,且低表达于不同病理类型的肺癌组织。Western blot检测发现,肺癌组织中FOXO3蛋白表达水平较正常肺组织显著下调(P <0. 01);肺癌干细胞中FOXO3蛋白表达水平较正常肺组织亦显著下调(P <0. 01)。RT-PCR检测发现,肺癌组织中FOXO3 mRNA相对表达量较正常肺组织显著降低(P <0. 01);肺癌干细胞中FOXO3 mRNA相对表达量较正常肺组织亦显著降低(P <0. 01)。不同病理类型的肺癌患者FOXO3蛋白阳性率的比较,差异无统计学意义(P>0. 05);未分化+低分化、伴有淋巴结转移的患者FOXO3蛋白阳性率较中分化+高分化、无淋巴结转移者显著降低(P<0. 05)。结论肺癌组织与肺癌干细胞中FOXO3具有低表达的特点,并且其与肺癌分化程度和淋巴结转移存在密切关系,FOXO3有望成为临床治疗肺癌患者的新型靶点,具有潜在的研究价值。
Objective To analyze the expression of FOXO3 in lung cancer tissues and lung cancer stem cells and its correlation with differentiation and metastasis of lung cancer. Methods The clinical data of 105 patients with lung cancer in our hospital were retrospectively analyzed and compared with 35 cases of normal lung tissue specimens. The expression of FOXO3 in lung cancer tissues and normal lung tissues was detected by immunohistochemistry,Western blot and reverse transcription-polymerase chain reaction( RT-PCR). The expression levels of FOXO3 protein and mRNA in lung cancer stem cells were detected by Western blot and RT-PCR. At the same time,lung cancer patients with different pathological types,differentiation degree and lymph node metastasis were compared. The expression of FOXO3 protein in the patients.Results Immunohistochemistry showed that FOXO3 protein was mainly localized in cytoplasm and interstitium,and was low expressed in lung cancer tissues of different pathological types. Western blot showed that the expression of FOXO3 in lung cancer tissues was significantly lower than that in normal lung tissues( P < 0. 01). The expression of FOXO3 in lung cancer stem cells was also significantly lower than that in normal lung tissues( P < 0. 01). RT-PCR showed that the relative expression of FOXO 3 in lung cancer tissues was significantly lower than that in normal lung tissues( P < 0. 01). The relative expression of FOXO 3 in lung cancer stem cells was also significantly lower than that in normal lung tissues( P < 0. 01). The positive rate of FOXO3 protein in lung cancer patients with different pathological types had no statistical significance( P >0. 05). The positive rate of FOXO3 protein in undifferentiated + poorly differentiated patients with lymph node metastasis was significantly lower than that in moderately differentiated + highly differentiated patients without lymph node metastasis( P < 0. 05). Conclusion FOXO3 expression in lung cancer tissues and lung cancer stem cells is low,and it is closely related to the degree of differentiation and lymph node metastasis of lung cancer. It is expected to become a new target for clinical treatment of lung cancer patients and has potential research value.
Objective To analyze the expression of FOXO3 in lung cancer tissues and lung cancer stem cells and its correlation with differentiation and metastasis of lung cancer. Methods The clinical data of 105 patients with lung cancer in our hospital were retrospectively analyzed and compared with 35 cases of normal lung tissue specimens. The expression of FOXO3 in lung cancer tissues and normal lung tissues was detected by immunohistochemistry,Western blot and reverse transcription-polymerase chain reaction( RT-PCR). The expression levels of FOXO3 protein and mRNA in lung cancer stem cells were detected by Western blot and RT-PCR. At the same time,lung cancer patients with different pathological types,differentiation degree and lymph node metastasis were compared. The expression of FOXO3 protein in the patients.Results Immunohistochemistry showed that FOXO3 protein was mainly localized in cytoplasm and interstitium,and was low expressed in lung cancer tissues of different pathological types. Western blot showed that the expression of FOXO3 in lung cancer tissues was significantly lower than that in normal lung tissues( P < 0. 01). The expression of FOXO3 in lung cancer stem cells was also significantly lower than that in normal lung tissues( P < 0. 01). RT-PCR showed that the relative expression of FOXO 3 in lung cancer tissues was significantly lower than that in normal lung tissues( P < 0. 01). The relative expression of FOXO 3 in lung cancer stem cells was also significantly lower than that in normal lung tissues( P < 0. 01). The positive rate of FOXO3 protein in lung cancer patients with different pathological types had no statistical significance( P >0. 05). The positive rate of FOXO3 protein in undifferentiated + poorly differentiated patients with lymph node metastasis was significantly lower than that in moderately differentiated + highly differentiated patients without lymph node metastasis( P < 0. 05). Conclusion FOXO3 expression in lung cancer tissues and lung cancer stem cells is low,and it is closely related to the degree of differentiation and lymph node metastasis of lung cancer. It is expected to become a new target for clinical treatment of lung cancer patients and has potential research value.
引文
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[15]寿铸,何丹.鼻咽癌组织中转录因子FOXO3a、HIF-1α蛋白及mRNA表达及意义[J].山东医药,2015,55(28):73-75,111.
[16]Sobolesky PM,Halushka PV,Garrett-Mayer E,et al.Regulation of the tumor suppressor FOXO3 by the thromboxane-A2 receptors in urothelial cancer[J].PLo S One,2014,9(9):e107530.
[2]刘红岗,赖远阳,朱以芳,等.JNK/FOXO3信号通路介导黄连素促人肺腺癌PC-9细胞凋亡的研究[J].中国肿瘤临床,2017,44(17):846-850.
[3]张庚艳.FOXO3基因与肿瘤的研究进展[J].临床肺科杂志,2017,22(5):919-922.
[4]刘鑫,胡皆乐,李佑,等.FOXO3在结直肠癌组织中的表达及临床意义[J].实用癌症杂志,2016,31(11):1773-1777.
[5]姚晓军,刘伦旭.肺癌的流行病学及治疗现状[J].现代肿瘤医学,2014,22(8):1982-1986.
[6]Ma W,Kang Y,Ning L,et al.Identification of microRNAs involved in gefitinib resistance of non-small-cell lung cancer through the insulin-like growth factor receptor 1 signaling pathway[J].Exp Ther Med,2017,14(4):2853-2862.
[7]Deng SM,Yan XC,Liang L,et al.The Notch ligand delta-like 3 promotes tumor growth and inhibits Notch signaling in lung cancer cells in mice[J].Biochem Biophys Res Commun,2017,483(1):488-494.
[8]Zhang WL,Zhao YN,Shi ZZ,et al.Lutein inhibits cell growth and activates apoptosis via the PI3K/AKT/m TOR signaling pathway in A549human non-small-cell lung cancer cells[J].J Environ Pathol Toxicol Oncol,2018,37(4):341-350.
[9]Feng CC,Lin CC,Lai YP,et al.Hypoxia suppresses myocardial survival pathway through HIF-1α-IGFBP-3-dependent signaling and enhances cardiomyocyte autophagic and apoptotic effects mainly via Fox O3a-induced BNIP3 expression[J].Growth Factors,2016,34(3-4):73-86.
[10]Ye K.Inhibition of IκB kinase in Notch signaling activates FOXO3a[J].Cell Cycle,2012,11(13):2417.
[11]Lin CH,Lin CC,Ting WJ,et al.Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts[J].Age(Dordr),2014,36(5):9705.
[12]Salcher S,Hagenbuchner J,Geiger K,et al.C10ORF10/DEPP,a transcriptional target of FOXO3,regulates ROS-sensitivity in human neuroblastoma[J].Mol Cancer,2014,13:224.
[13]韩燕燕,张琳,程慧敏,等.FOXO3a在三氧化二砷影响大肠癌细胞β-catenin表达中的作用[J].徐州医学院学报,2014,34(4):258-261.
[14]刘嵬,王成,刘卫,等.Fox O3a对胆管癌细胞增殖及凋亡的影响[J].胃肠病学和肝病学杂志,2018,27(8):942-946.
[15]寿铸,何丹.鼻咽癌组织中转录因子FOXO3a、HIF-1α蛋白及mRNA表达及意义[J].山东医药,2015,55(28):73-75,111.
[16]Sobolesky PM,Halushka PV,Garrett-Mayer E,et al.Regulation of the tumor suppressor FOXO3 by the thromboxane-A2 receptors in urothelial cancer[J].PLo S One,2014,9(9):e107530.