厄洛替尼对非小细胞肺癌脑转移细胞PC14/B侵袭转移能力的抑制作用

Inhibition effects of erlotinib on invasion and metastasis in non-small cell lung cancer brain metastasis cell PC14/B

目的研究厄洛替尼对非小细胞肺癌(NSCLC)脑转移细胞PC14/B侵袭转移能力的抑制作用。方法 PC14/B细胞随机分为对照组及3个浓度实验组(厄洛替尼,1,5,25μmol·L^(-1)),噻唑蓝法和迁移小室法分别检测细胞活力及侵袭能力,免疫印迹法检测基质金属蛋白酶2(MMP2)、MMP9、上皮细胞-间充质转化(EMT)相关蛋白E-钙黏附素、波形蛋白的表达及蛋白激酶B(AKT)磷酸化水平。结果与对照组(0.75±0.09)比较,小中大3个浓度实验组均能显著抑制PC14/B细胞活力,比值分别为(0.63±0.06),(0.52±0.04),(0.38±0.03)。与对照组比较,3个浓度实验组均能显著降低侵袭力,上调E-钙黏附素表达,下调MMP2、MMP9及波形蛋白表达,并降低AKT磷酸化水平。结论厄洛替尼能显著的抑制PC14/B细胞侵袭转移能力,与下调MMPs表达、抑制EMT生成及降低AKT磷酸化水平有关。

Obejective To explore the inhibition effects of erlotinib on invasion and metastasis in non - small cell lung cancer brain metastasis cell PC14/B. Methods MTT method was used to detect the viability of PC14/B cells 48 h after the cultivation with erlotinib of 0 （control group）, 1, 5 and 25 μmol . L -1 （erlotinib , test groups）. The cell inva- sion was detected by tranaswell method. The phosphorylation of protein kinase B （AKT） and the expression of matrix metalloproteinase 2 （ MMP2 ） , MMP9 epithelial - mesenchymal transition （ EMT ） related proteins including E -cadhherin and Vimentin were detected by Western blot. Results Compared with control group （0. 75 ± 0.09）, three dose test groups[ （0. 63 ±0, 06）, （0. 52 ±0.04）, （0. 38 ±0.03） ] inhibited the cell viability. Compared with control group, three dose test groups inhibited invasion, up - regulated the expression of E - cadherin, and down- regulated the expressions of MMP2, MMPg, Vimentin and the phosphorylation of AKT. Conclusion Erlotinib suppressed PC14/B cell invasion and metastasis, which was related to the down - regulation of the expression of MMPs, and the inhibition on the generation of EMT and the phosphorylation of AKT. Key words： erlotinib; non- small cell lung cancer brain metastasis cell PC14/B; invasion; metastasis