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.
展开▼
