摘要
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.
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2015年第2期105-111,共7页
China Oncology
基金
湖北省自然科学基金青年项目(2013CFB370)