Abstract:
Objective To investigate the expression of brain-derived neurotrophic factor (BDNF) and its primary receptor, tropomysin-related kinase B (TrkB) in hepatocellular carcinoma (HCC) tissues, and to evaluate the functions of these proteins in the oncogenesis and progression of HCC.
Methods The expression of BDNF and TrkB in 65 HCC cases was evaluated via immunohistochemical staining. In the human HCC HepG2 cell lines, the secretory BDNF in the supernatant liquid was measured using enzyme-linked immunosorbent assay (ELISA). The effects of BDNF-neutralizing antibody and the Trk tyrosine kinase inhibitor K252a on apoptosis and invasion were examined using flow cytometry and a Transwell assay, respectively.
Results Higher BDNF expression (63.1%) or positive TrkB expression (55.4%) was found in the HCC specimens. More cases of intrahepatic multiple tumors were found in HCCs with higher BDNF expression (P < 0.01). Similarly, HCCs with negative for TrkB tended to be solitary tumors (P < 0.05). In addition, patients with higher levels of BDNF expression or positive TrkB expression had more advanced stages of HCC (P < 0.05). The level of BDNF secretion in HepG2 cells was 88.56 pg/ml±7.45 pg/ml. Both anti-BDNF and K252a antibodies effectively induced apoptosis and suppressed the invasion of the HepG2 cells.
Conclusion BDNF and TrkB are essential for the survival and invasion of the HCC cells. BDNF/TrkB signaling may be an effective target for promoting HCC advancement.
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