Abstract:

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