激活蛋白酶活化受体2抑制肺癌细胞凋亡

Activation of protease-activated receptor 2 inhibits apoptosis of lung cancer cells

目的观察蛋白酶激活受体2(PAR2)活化对肺癌细胞株A549表皮生长因子受体(EGFR)表达及凋亡影响。方法在A549及EGFR基因沉默的A549细胞株培养液中加入类胰蛋白酶,用定量RT-PCR及Western blot法检测EGFR表达,观测细胞凋亡情况及与Bax/Bcl-xL表达水平。结果与类胰蛋白酶共培养48 h后,A549细胞EGFR表达明显增加。凋亡比例明显降低,而且这种降低呈现剂量浓度依赖性。细胞中Bax表达明显减少而Bcl-xL明显增加。EGFR基因沉默后,类胰蛋白酶对A549细胞凋亡的抑制作用被阻断,对Bax/Bcl-xL比率亦无影响。结论类胰蛋白酶能增加肺癌细胞株A549EGFR表达,减少其凋亡,明显减少Bax表达而增加Bcl-xL表达。

Aim To investigate the activation of protease-activated receptor 2 （PAR2） in regulation of the expression of epidermal growth factor receptor （EGFR） and apoptosis of lung cancer （LC） cells. Methods LC cells A549 and its EGFR-silenced counterpart were incubated in the medium added with tryptase. Quantitative RT-PCR and Western blotting were used to detect the expression of EGFR in A 5 4 9 cells. The apoptosis and Bax/Bcl-xL of ceils were also recorded. Results Treating A549 ceils with tryptase in the culture for 48 hrs resulted in a marked increase in the expression of EGFR in A549 cells. Marked decreases in a tryptase dose-dependent manner in apoptotic A549 cells were detected in the presence of tryptase. Exposure to tryptase markedly decreased the levels of Bax and increased the levels of Bcl-xL in A549 cells,which were not shown in EGFR-deficient A549 cells. Conclusion Tryptase can increase the expression of EGFR in LC cell line, A549 cells, which protects A549 ceils from apoptosis, increases Bel-xL, and suppresses Bax in A549 cells.