rhIL-11通过激活JAK/STAT3/HIF-1α/EMT通路促进肺腺癌A549细胞转移机制

rhIL-11 promotes lung adenocarcinoma A549 cell metastasis by activating JAK/STAT3/HIF 1 α/EMT pathway

目的探讨重组人白细胞介素11(rhIL-11)通过激活JAK/STAT3/HIF-1α/EMT通路促进肺腺癌A549细胞侵袭转移的机制。方法将人肺腺癌A549细胞分为rhIL-11 0μg/L组(对照组)、rhIL-11 10μg/L组、rhIL-11 40μg/L组、rhIL-11 80μg/L组、rhIL-11 0μg/L+AG490(JAK抑制剂)组、rhIL-11 10μg/L+AG490组、rhIL-11 40μg/L+AG490组和rhIL-11 80μg/L+AG490组共8组,采用划痕试验和Transwell侵袭试验了解rhIL-11对细胞迁移和侵袭能力的影响。用qRT-PCR和Western Blot法检测肿瘤细胞中STAT3、HIF-1α、Twist和E-Cadherin等基因的mRNA和蛋白表达。结果 rhIL-11促进肺癌A549细胞迁移和侵袭能力增强,且随着rhIL-11浓度的增高而增强,各组间比较,差异均有统计学意义(P<0.05)。与对照组比较,rhIL-11 80μg/L组的STAT3、HIF-1α和Twist等基因的mRNA和蛋白表达量均明显增加(P<0.05),而E-Cadherin基因的mRNA和蛋白表达量均明显减低(P<0.05)。与rhIL-11 80μg/L组比较,rhIL-11 80μg/L+AG490组的STAT3、HIF-1α和Twist的mRNA和蛋白表达均显著降低(P<0.01)。结论 rhIL-11促进肺癌A549细胞侵袭转移,其机制可能是通过激活JAK/STAT3/HIF-1α/EMT信号通路促进转移。

Objective To investigate the mechanism of recombinant human interleukin-11(rhIL-11) promoting the invasion and metastasis of lung adenocarcinoma A549 cells by activating JAK/STAT3/HIF-1 α/EMT pathway. Methods Human lung adenocarcinoma A549 cells were divided into rhIL 11 0 μg/L Group(control group), rhIL 11 0μg/L group, rhIL 11 40 μ/l group, rhIL 11 80 μg/L group, rhIL 11 0 μg/L + AG490(JAK inhibitor) group, rhIL 11 10 μ g/L+ AG490 group, rhIL 11 40μg/L + AG490 group and rhIL 11 80μg/L+ AG490 group. The effects of rhIL 11 on cell migration and invasion were studied by scratch test and Transwell invasion test. The mRNA and protein expression of STAT3, HIF 1 α, twist and E cadherin were detected by QRT PCR and Western blot. Results rhIL 11 promoted the migration and invasion of lung cancer A549 cells. Compared with the control group, the mRNA and protein expression of STAT3, HIF 1 α and twist genes in rhIL 11 80 μ g/L group increased significantly(P<0.05), while the mRNA and protein expression of E cadherin gene decreased significantly(P<0.05). Compared with rhIL 11 80 μg/L group, the mRNA and protein expression of STAT3, HIF 1 α and twist in rhIL 11 80 μg/L+AG490 group decreased significantly(P<0.01). Conclusion rhIL 11 promotes the invasion and metastasis of lung cancer A549 cells, which may be due to the activation of JAK/STAT3/HIF 1 α/EMT signaling pathway.