高迁移率族蛋白B1激活NF-κB/αvβ3而增加A549细胞迁移与侵袭能力

HMGB1 activates NF-κB/αvβ3 to promote A549 cells migration and invasion

背景与目的:高迁移率族蛋白B1(high mobility group box 1,HMGB1)在多种肿瘤中高表达,在肿瘤的侵袭转移中发挥重要作用。本研究旨在探讨HMGB1促进肺癌A549细胞侵袭的分子机制。方法:肺癌A549细胞经HMGB1,NF-κB抑制剂6-amino-4-quinazoline(QNZ)或Bortezomib(Bort)处理后,划痕实验和Transwell小室体外侵袭实验检测肿瘤细胞的迁移及侵袭能力;NF-κB荧光素酶报告基因实验检测NF-κB活性;Real-time RT-PCR和Western blot检测A549细胞NF-κB和整合素αvβ3表达。结果:HMGB1能增强A549细胞迁移和侵袭能力,增加NF-κBp65蛋白的表达,同时增强A549细胞NF-κB活性,Real-time RT-PCR和Western blot检测结果发现HMGB1上调肿瘤细胞αvβ3表达。NF-κB抑制剂QNZ或Bort消除HMGB1促进A549细胞迁移及侵袭,增强NF-κB表达和活性以及αvβ3表达的效应。结论:HMGB1通过激活A549细胞NF-κB上调αvβ3表达促进A549细胞迁移与侵袭行为。

Background and purpose：High mobility group 1 （HMGB1）, frequently found to be over-expressed in many human tumors, plays an important role in tumor progress and metastasis. This study aimed to investigate the mechanism of HMGB1 promoting A549 cell metastasis.Methods：A549 cells were untreated or treated with HMGB1 （200 ng/mL） in absence or presence of NF-κB inhibitors 6-amino-4-quinazoline （QNZ, 40 nmol/L） or Bortezomib （Bort, 20 nmol/L）. Scratch assay and Transwell assay were performed to evaluate A549 cells migration and invasion ability. The activity of NF-κB was examined by luciferase reporter assay. NF-κBp65 and αvβ3 expressions were detected by Real-time RT-PCR or Western blot.Results：HMGB1 increased A549 cells migration and invasion ability. HMGB1 enhanced NF-κB protein level and NF-κB activity in A549 cells. Real-time RT-PCR and Western blot showed that HMGB1 up-regulated αvβ3 expression in A549 cells. NF-κB inhibitors QNZ or Bort reserved the promot-ing effects of HMGB1 on A549 cells migration and invasion, NF-κB expression and activity as well as αvβ3 expression. Conclusion：HMGB1 promotes A549 cell migration and invasion through activating NF-κB and up-regulating αvβ3.