本文選題：DNAJ熱激蛋白家族B　切入點(diǎn)：肺腺癌　出處：《中國腫瘤生物治療雜志》2017年08期 　論文類型：期刊論文

【摘要】：目的:探討DNAJ熱激蛋白家族B8基因(DNAJ heat shock protein family member B8,DNAJB8)在肺腺癌組織中的表達(dá)及其對(duì)肺腺癌細(xì)胞侵襲轉(zhuǎn)移的作用和可能機(jī)制。方法:收集四川省人民醫(yī)院2006年至2008年的肺腺癌手術(shù)切除標(biāo)本102例,通過免疫組織化學(xué)(IHC)實(shí)驗(yàn)檢測(cè)DNAJB8在肺腺癌組織中的表達(dá)情況,并分析其與臨床病理參數(shù)及預(yù)后的關(guān)系。構(gòu)建DNAJB8穩(wěn)定敲低的肺腺癌A549細(xì)胞和DNAJB8穩(wěn)定過表達(dá)的肺腺癌H1299細(xì)胞,CCK-8實(shí)驗(yàn)檢測(cè)DNAJB8敲降或過表達(dá)對(duì)肺腺癌細(xì)胞增殖的影響,Transwell法檢測(cè)其對(duì)肺腺癌細(xì)胞侵襲能力的影響,Western blotting檢測(cè)其對(duì)肺腺癌細(xì)胞內(nèi)侵襲相關(guān)蛋白MMP-2、MMP-9和ERK表達(dá)及活性的影響。裸鼠尾靜脈注射DNAJB8穩(wěn)定敲低的A549細(xì)胞構(gòu)建肺腺癌轉(zhuǎn)移模型,觀察DNAJB8對(duì)A549細(xì)胞體內(nèi)轉(zhuǎn)移能力的影響。結(jié)果:DNAJB8在肺腺癌組織中的表達(dá)明顯高于正常肺組織,其高表達(dá)與患者的淋巴結(jié)轉(zhuǎn)移及TNM分期呈正相關(guān),并且預(yù)示著患者有較差的預(yù)后(均P0.01)。DNAJB8在A549細(xì)胞中的表達(dá)量高于H1299細(xì)胞,下調(diào)DNAJB8表達(dá)能夠抑制A549細(xì)胞的侵襲[(41±3)vs(192±11)個(gè),P0.01],而上調(diào)DNAJB8的表達(dá)能夠促進(jìn)H1299細(xì)胞的侵襲[(235±14)vs(25±4)個(gè),P0.01]。實(shí)驗(yàn)組肺腺癌轉(zhuǎn)移模型裸鼠肺臟腫瘤結(jié)節(jié)數(shù)顯著低于對(duì)照組[(5±1)vs(17±3)個(gè),P0.01]。A549細(xì)胞中DNAJB8敲降后,MMP-2、MMP-9表達(dá)量和p-ERK水平均顯著下降(均P0.01);而H1299細(xì)胞高表達(dá)DNAJB8后,MMP-2、MMP-9表達(dá)量和p-ERK水平均顯著升高(均P0.01)。結(jié)論:DNAJB8能夠促進(jìn)肺腺癌的侵襲和轉(zhuǎn)移,其機(jī)制可能與MEK/Erk信號(hào)通路有關(guān)。
[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 鹵3 VSD 192 鹵11], while up-regulation of DNAJB8 expression could promote the invasion of H1299 cells [235 鹵14 vs 25 鹵4]. The number of nodule in lung tumor of nude mice in experimental group was significantly lower than that in control group [5 鹵1 vs 17 鹵3] .A549 cells in the experimental group were significantly lower than those in the control group [5 鹵1 vs 17 鹵3] .A549 cells in the experimental group were significantly lower than those in the control group [5 鹵1 vs 17 鹵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.
【作者單位】： 四川省醫(yī)學(xué)科學(xué)院暨四川省人民醫(yī)院腫瘤中心;
【基金】：四川省科技發(fā)展基金資助(No.2014JY0136)~~
【分類號(hào)】：R734.2

【參考文獻(xiàn)】

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