OPG/RANKL/RANK轴在非小细胞肺癌发生及淋巴转移中的作用
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江苏省卫生厅面上项目(H200708)


The effect of OPG/RANKL/RANK axis on the pathogenesis and lymphatic metastasis in patients with non-small cell lung cancer
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    摘要:

    目的:检测OPG/RANKL/RANK轴在非小细胞肺癌(NSCLC)中的表达及NF-κB 的活性和含量,进而探讨其临床意义-方法:以15例正常肺组织为对照,采用实时荧光定量PCR方法,检测17例腺癌和15例鳞癌及其癌旁组织中 OPG-RANKL-RANK mRNA的表达量,并用免疫印迹的方法检测核蛋白和总蛋白中NF-κB p65的含量-结果:① OPG-RANKL-RANK mRNA的表达量及 RANKL/OPG比值在正常肺-NSCLC 癌旁和癌组织中呈梯度升高,差异均有统计学意义-② 在有淋巴结转移病例(n=19)的癌组织中 OPG-RANKL-RANK mRNA的表达量及 RANKL/OPG比值均显著高于无淋巴结转移的病例(n=13)-③ 在肺癌-癌旁及正常肺组织中,NF-κB p65核/总蛋白含量之比依次降低,差异有显著性-④ NF-κB p65核/总蛋白含量之比在有淋巴结转移的癌组织要显著高于无淋巴结转移的癌组织-结论:在人NSCLC中,OPG/RANKL/RANK轴的激活进一步激活 NF-κB信号通路,可能在肿瘤的发生和淋巴转移中起重要作用-

    Abstract:

    Objective:To investigate the expression levels of OPG,RANKL,RANK,and the level and activity of NF-κB p65 in patients with non-small cell lung cancer(NSCLC),then to explore their clinical significance. Methods:The gene expression levels of OPG,RANKL,RANKwere assessed by real-time PCR and the level and activity of NF-κB by western blot in cancer and corresponding adjacent lung tissues of 32 NSCLC patients and normal lung tissues of 15 chest trauma or inflammation patients matched. Results:A significant increasing gradient of gene expression of OPG,RANKL,RANK and RANKL/OPG ratio was identified in normal,adjacent lung tissues of NSCLC and cancer tissues,as well as the intranuclear/total ratio of NF-κB p65,whereas the level of total NF-κB p65 was comparable among the three groups. Moreover,the mRNA levels and RANKL/OPG ratio of the axis in cancer tissues of NSCLC with lymph node metastasis was significantly higher than that in NSCLC without lymph node metastasis. The intranuclear/total ratio of NF-κB p65,but not the total level,was also increased notably in cancer tissues of NSCLC with lymph node metastasis. Conclusion:The activation of OPG/RANKL/RANK axis may play an important role in pathogenesis and lymphatic metastasis of human NSCLC through activating the NF-κB signal transduction pathway.

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李明娜,曹海龙,范钦和. OPG/RANKL/RANK轴在非小细胞肺癌发生及淋巴转移中的作用[J].南京医科大学学报(自然科学版),2010,(5):662-666

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