China Oncology ›› 2017, Vol. 27 ›› Issue (10): 761-769.doi: 10.19401/j.cnki.1007-3639.2017.10.001

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Role of HMGB1/TLR4 pathway in the process of Fibulin-5 inhibiting lung cancer cells proliferation and metastasis

ZHANG Xiaojuan, WANG Huijuan, ZHANG Mina, ZHANG Guowei   

  1. Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, Henan Province, China
  • Online:2017-10-30 Published:2017-12-05
  • Contact: ZHANG Xiaojuan E-mail:


Background and purpose: The expression of Fibulin-5, a tumor suppressor, is reduced in lung cancer tissues. High mobility group box 1 (HMGB1), overexpressed in lung cancer, can promote the invasion and metastasis of the tumor. This study aimed to investigate the molecular mechanism of Fibulin-5 inhibiting the proliferation and metastasis of lung cancer cells. Method: Firstly the expressions of Fibulin-5 and HMGB1 in lung epithelial cells and lung cancer cells were detected. Then transfection reagents were used to transfect Fibulin-5 plasmid and HMGB1 siRNA into A549 cells, which achieved Fibulin-5 overexpression and HMGB1 down-regulation. MTT was used to detect the cell proliferation. Transwell was used to examine the ability of cell invasion and migration. HMGB1 mRNA expression was detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). The secretion of HMGB1 protein was analyzed by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the levels of HMGB1, cyclin D1, matrix metalloproteinases (MMPs), and TLR4/NF-κB pathway related proteins. Results: In A549 cell, Fibulin-5 expression was down-regulated and HMGB1 expression was up-regulated. After overexpression of Fibulin-5 or knockdown of HMGB1 in A549 cells, the levels of HMGB1, cyclin D1, MMP2, MMP7 and MMP9 were significantly reduced; the abilities of lung cancer cell proliferation, invasion and migration were notably suppressed (P<0.05). In addition, Fibulin-5 overexpression decreased the protein expressions of TLR4, MyD88, p-p65, increased the expression of IκBα (P<0.05). Conclusion: Fibulin-5 may inhibit lung cancer cell proliferation, invasion and migration via inhibiting the expression of HMGB1 and its downstream TLR4/NF-κB pathway.

Key words: Fibulin 5, High mobility group box 1, TLR4/NF-κB pathway, Lung cancer, Invasion, Migration