Background & objective: Metastasis is one of the important reasons for treatment failure of hepatocellular carcinoma (HCC). It is related to biologic behaviors of HCC, including proliferation, migration, and invasion. Recently, researchers have realized that brain-derived neurotrophic factor (BDNF) is a functional protein that exists in HCC tissue, and closely relates to the development of HCC, but the exact mechanism is still unknown. This study was to explore the effect of BDNF on in vitro metastasis of HCC cell line HepG2, and investigate its mechanism.
Methods: The effect of BDNF on the proliferation of HepG2 cells was examined by MTT assay. The effect of BDNF on the metastasis of HepG2 cells was evaluated by tumor cell migration and invasion assays. The expression of TrkB, a specific receptor of BDNF, in HepG2 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.
Results: BDNF efficiently stimulated the proliferation of HepG2 cells in a dose-dependent manner under the concentration of 100 ng/ml. The migration index was significantly higher in the cells treated with 50 or 100 ng/ml BDNF than in control cells (167 and 203 vs. 100, P<0.05). Cell number on the down-side of transwell membrane was significantly higher in the cells treated with 50 or 100 ng/ml BDNF than in control cells (167+/-38 and 215+/-51 vs. 113+/-22, P<0.05). The expression of TrkB was higher in HepG2 than in normal liver cell line L-02.
Conclusions: BDNF can enhance the proliferation, migration, and invasion abilities of HCC cells. It is a novel cytokine which induces metastasis of HCC.