發(fā)布時(shí)間：2018-05-08 09:58

  本文選題：縫隙連接蛋白 + 非小細(xì)胞肺癌��； 參考：《重慶醫(yī)科大學(xué)學(xué)報(bào)》2017年11期

【摘要】：目的:探討縫隙連接蛋白43(connexin 43,Cx43)對(duì)非小細(xì)胞肺癌(non-small-cell lung cancer,NSCLC)吉非替尼原發(fā)性耐藥的影響。方法:MTT法測(cè)定吉非替尼對(duì)3株非突變型EGFR(WT-EGFR)NSCLC細(xì)胞系A(chǔ)549、H1299、Calu3細(xì)胞的半數(shù)抑制濃度(IC50);Western blot觀察Cx43、磷酸化Akt(phospho-Akt,p-Akt)蛋白在上述細(xì)胞系中的表達(dá)水平;"Parachute"法檢測(cè)細(xì)胞縫隙連接功能(gap junction intercellular communication,GJIC);免疫熒光法檢測(cè)Cx43蛋白在細(xì)胞中的定位。結(jié)果:吉非替尼作用于Calu3、A549、H1299細(xì)胞的IC50分別為(0.064±0.011)μmol/L、(13.64±0.015)μmol/L、(20.054±0.012)μmol/L,即A549、H1299細(xì)胞對(duì)吉非替尼原發(fā)性耐藥;A549、H1299細(xì)胞中Cx43、p-Akt蛋白水平顯著高于Calu3細(xì)胞(P0.01);A549、H1299細(xì)胞有熒光傳遞現(xiàn)象,且Cx43蛋白定位在A549、H1299細(xì)胞膜上,而Calu3細(xì)胞無(wú)熒光傳遞現(xiàn)象,且Cx43主要表達(dá)于細(xì)胞質(zhì)上。結(jié)論:NSCLC細(xì)胞膜上調(diào)的Cx43及其組成的GJIC可促進(jìn)細(xì)胞對(duì)吉非替尼的原發(fā)性耐藥,其機(jī)制可能與其激活PI3K/Akt信號(hào)通路有關(guān)。
[Abstract]:Objective: to investigate the effect of gap junction protein (43(connexin 43) on primary drug resistance of non-small cell lung cancer (NSCLC) in patients with non small cell lung cancer (NSCC). Methods the expression of Cx43, phosphorylated Aktophospho-Aktna-p-Akt protein in three non-mutant EGFR(WT-EGFR)NSCLC cell lines A549H 129- Calu3 cell line was detected by Western blot, the expression of Cx43, phosphorylated Aktphospho-Aktophospho-Aktnp-Akt protein was detected by "Parachute" method, the gap junction intercellular communication was detected by "Parachute" method, and the expression of Cx43, phosphorylated Aktophospho-Aktophosphor-Aktp-Akt protein was detected by "Parachute" method. The localization of Cx43 protein in cells was detected by immunofluorescence assay. Results: the levels of IC50 in Cx43H1299 cells were significantly higher than those in Calu3 cells (P0.01, A549H1299 cells), and the fluorescence transfer of Cx43 protein was observed in A549H1299 cells. The results showed that the expression of Cx43 protein in A549H1299 cells was significantly higher than that in P0.01A549H1299 cells, and the Cx43 protein was localized on the A549H1299 cell membrane, and the expression of Cx43 protein was located on the A549H1299 cell membrane, and the protein level of A549H1299 cells was significantly higher than that of the Cx43p-Akt cells of Cx43p-Akt cells. The results showed that the expression of Cx43 protein was localized on the cell membrane of A549H1299 cells, and the expression of Cx43 protein was localized on the A549H1299 cell membrane of A549H1299 cells. However, there was no fluorescence transfer in Calu3 cells, and Cx43 was mainly expressed in cytoplasm. Conclusion the up-regulated Cx43 and its component GJIC can promote the primary resistance to gifitinib, and the mechanism may be related to the activation of PI3K/Akt signaling pathway.
【作者單位】： 廣西醫(yī)科大學(xué)藥學(xué)院藥理學(xué)教研室;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(編號(hào):81260324) 教育部高等學(xué)校博士學(xué)科點(diǎn)專項(xiàng)科研基金新教師類資助項(xiàng)目(編號(hào):20124503120008)
【分類號(hào)】：R734.2
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本文編號(hào)：1860946