DNAJ热激蛋白家族B8基因对肺腺癌侵袭转移的作用及其可能的机制

发布时间：2018-03-17 04:28

本文选题：DNAJ热激蛋白家族B　切入点：肺腺癌　出处：《中国肿瘤生物治疗杂志》2017年08期 　论文类型：期刊论文

【摘要】：目的:探讨DNAJ热激蛋白家族B8基因(DNAJ heat shock protein family member B8,DNAJB8)在肺腺癌组织中的表达及其对肺腺癌细胞侵袭转移的作用和可能机制。方法:收集四川省人民医院2006年至2008年的肺腺癌手术切除标本102例,通过免疫组织化学(IHC)实验检测DNAJB8在肺腺癌组织中的表达情况,并分析其与临床病理参数及预后的关系。构建DNAJB8稳定敲低的肺腺癌A549细胞和DNAJB8稳定过表达的肺腺癌H1299细胞,CCK-8实验检测DNAJB8敲降或过表达对肺腺癌细胞增殖的影响,Transwell法检测其对肺腺癌细胞侵袭能力的影响,Western blotting检测其对肺腺癌细胞内侵袭相关蛋白MMP-2、MMP-9和ERK表达及活性的影响。裸鼠尾静脉注射DNAJB8稳定敲低的A549细胞构建肺腺癌转移模型,观察DNAJB8对A549细胞体内转移能力的影响。结果:DNAJB8在肺腺癌组织中的表达明显高于正常肺组织,其高表达与患者的淋巴结转移及TNM分期呈正相关,并且预示着患者有较差的预后(均P0.01)。DNAJB8在A549细胞中的表达量高于H1299细胞,下调DNAJB8表达能够抑制A549细胞的侵袭[(41±3)vs(192±11)个,P0.01],而上调DNAJB8的表达能够促进H1299细胞的侵袭[(235±14)vs(25±4)个,P0.01]。实验组肺腺癌转移模型裸鼠肺脏肿瘤结节数显著低于对照组[(5±1)vs(17±3)个,P0.01]。A549细胞中DNAJB8敲降后,MMP-2、MMP-9表达量和p-ERK水平均显著下降(均P0.01);而H1299细胞高表达DNAJB8后,MMP-2、MMP-9表达量和p-ERK水平均显著升高(均P0.01)。结论:DNAJB8能够促进肺腺癌的侵袭和转移,其机制可能与MEK/Erk信号通路有关。
[Abstract]:Objective: to investigate the expression of DNAJ heat J heat shock protein family member B8 gene JB8 in lung adenocarcinoma and its role in invasion and metastasis of lung adenocarcinoma cells. Methods: from 2006 to 2008 in Sichuan Provincial people's Hospital. A total of 102 cases of lung adenocarcinoma were surgically resected. The expression of DNAJB8 in lung adenocarcinoma was detected by immunohistochemistry assay. The relationship between CCK-8 and clinicopathological parameters and prognosis of lung adenocarcinoma A549 cells with stable knockout of DNAJB8 and H1299 cells with stable overexpression of DNAJB8 was constructed to detect the effect of DNAJB8 knockdown or overexpression on proliferation of lung adenocarcinoma cells. The effect of blotting on the expression and activity of MMP-2MMP 9 and ERK in lung adenocarcinoma cells was determined by Western blotting. The metastatic model of lung adenocarcinoma was established by injecting DNAJB8 stable knockdown A549 cells into tail vein of nude mice. Results the expression of DNAJB8 JB8 in lung adenocarcinoma was significantly higher than that in normal lung tissue. The high expression of DNAJB8 was positively correlated with lymph node metastasis and TNM stage. The expression of DNA JB8 in A549 cells was higher than that in H1299 cells. Down-regulation of DNAJB8 expression could inhibit the invasion of A549 cells [41 卤3 VSD 192 卤11], while up-regulation of DNAJB8 expression could promote the invasion of H1299 cells [235 卤14 vs 25 卤4]. The number of nodule in lung tumor of nude mice in experimental group was significantly lower than that in control group [5 卤1 vs 17 卤3] .A549 cells in the experimental group were significantly lower than those in the control group [5 卤1 vs 17 卤3] .A549 cells in the experimental group were significantly lower than those in the control group [5 卤1 vs 17 卤3] .A549 cells in the experimental group were significantly lower than those in the control group. After DNAJB8 knockdown, the expression of MMP-2, MMP-9 and p-ERK in H1299 cells decreased significantly (all P 0.01), while in H1299 cells, the expression of MMP-2, MMP-9 and p-ERK in H1299 cells increased significantly (all P 0.01). Conclusion: the expression of MMP-2MMP 9 and the level of p-ERK in H1299 cells can promote the invasion and metastasis of lung adenocarcinoma. The mechanism may be related to the MEK/Erk signaling pathway.
【作者单位】：四川省医学科学院暨四川省人民医院肿瘤中心;
【基金】：四川省科技发展基金资助(No.2014JY0136)~~
【分类号】：R734.2

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