丙泊酚抑制IL-6诱导的A549肺癌细胞上皮间质转化及其机制探讨

Propofol suppresses IL-6-induced epithelial-mesenchymal transition of A549 lung cancer cells and its mechanism research

目的:探究丙泊酚对白细胞介素-6(IL-6)诱导的A549肺癌细胞上皮间质转化(EMT)的作用及机制。方法:将A549细胞随机分成四组:对照组、IL-6组(50 ng/ml重组IL-6蛋白)、IL-6+丙泊酚低剂量组(50 ng/ml重组IL-6蛋白和5μmol/L丙泊酚)、IL-6+丙泊酚高剂量组(50 ng/ml重组IL-6蛋白和10μmol/L丙泊酚)。MTT法检测细胞活力,Transwell检测细胞迁移情况,Real-time PCR方法检测EMT相关基因(E-cadherin、Vimentin和Snail1)mRNA的表达水平,Western blot检测EMT相关蛋白及JAK2和STAT3的磷酸化表达水平。使用0.5μmol/L STAT3激活剂colivelin处理细胞,检测其对丙泊酚调节的IL-6诱导的A549细胞活力、迁移和EMT的影响。结果:与对照组相比,IL-6组中细胞的活力、迁移、EMT和JAK2/STAT3的活化均增加(P均<0.05);与IL-6组相比,IL-6+丙泊酚组中细胞活力、迁移、EMT和JAK2/STAT3的活化均降低(P均<0.05),这些变化均具有剂量依赖性。STAT3激活剂能够减弱丙泊酚对IL-6诱导的A549细胞活力、迁移和EMT的影响(P均<0.05)。结论:丙泊酚能够抑制IL-6诱导的A549肺癌细胞EMT进程,这种作用是通过抑制JAK2/STAT3的活化发挥作用的。

Objective： To investigate the role and mechanism of propofol on interleukin-6（ IL-6）-induced epithelial-mesenchymal transition（ EMT） of A549 lung cancer cells. Methods： A549 cells were randomly divided into four groups： Control group,IL-6 group（ 50 ng/ml recombinant IL-6 protein）,IL-6 ＋ propofol（ low） group（ 50 ng/ml recombinant IL-6 protein and 5 μmol/L propofol）,and IL-6 ＋ propofol（ high） group（ 50 ng/ml recombinant IL-6 protein and 10 μmol/L propofol）. MTT was used to analyze cell viability. Cell migration was determined by Transwell assay. Real-time PCR was used to detect the mRNA expression of EMT-related genes（ E-cadherin,Vimentin,and Snail1）. Western blot was used to measure the levels of EMT-related proteins and the phosphorylation of JAK2 and STAT3. Additionally,we also determined the role of 0. 5 μmol/L STAT3 activator colivelin on propofol-mediated the proliferation,migration,and EMT induced by IL-6. Results： Compared with control group,cell viability,migration,EMT,and the activation of JAK2/STAT3 were increased in IL-6 group（ P all 〈0. 05）. Compared with IL-6 group,cell viability,migration,EMT,and the activation of JAK2/STAT3 were decreased in IL-6 ＋ propofol group（ P all 〈0. 05） in a dose-dependent manner. STAT3 activator could attenuate the effect of propofol on IL-6-induced cell viability,migration,and EMT（ P all〈 0. 05）. Conclusion： Propofol could suppress IL-6-induced A549 lung cancer cell EMT via inhibiting the activation of JAK2/STAT3.