HMGB1 activates NF-κB/αvβ3 to promote A549 cells migration and invasion / 中国癌症杂志

ABSTRACT

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.