Department of General Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, China.
J Exp Clin Cancer Res. 2011 Oct 14;30(1):97. doi: 10.1186/1756-9966-30-97.
Brain-derived neurotrophic factor (BDNF) and its receptor Tropomysin-related kinase B (TrkB) are commonly up-regulated in a variety of human tumors. However, the roles of BDNF/TrkB in hepatocellular carcinoma (HCC) have been poorly investigated.
We evaluated the expressions of BDNF and TrkB in 65 cases of HCC by immunohistochemical staining. Moreover, in human HCC cell lines of HepG2 and high metastatic HCCLM3, the secretory BDNF in supernatant was measured by ELISA, the effects of BDNF neutralizing antibody or Trk tyrosine kinase inhibitor K252a on apoptosis and invasion were examined by flow cytometry and transwell assay respectively.
Higher expression of BDNF (63.1%) or positive expression of TrkB (55.4%) was found in HCC specimens, which was significantly correlated with multiple and advanced stage of HCC. BDNF secretory level in HCCLM3 was higher than that in HepG2 cells. Both anti-BDNF and K252a effectively induced apoptosis and suppressed invasion of HepG2 and HCCLM3 cells.
These findings suggested that BDNF/TrkB are essential for HCC cells survival and invasion. BDNF/TrkB signaling should probably be an effective target to prevent HCC advancement.
脑源性神经营养因子（BDNF）及其受体原肌球蛋白相关激酶 B（TrkB）在多种人类肿瘤中普遍上调。然而，BDNF/TrkB 在肝细胞癌（HCC）中的作用尚未得到充分研究。
我们通过免疫组织化学染色评估了 65 例 HCC 中 BDNF 和 TrkB 的表达。此外，在 HepG2 和高转移性 HCCLM3 人 HCC 细胞系中，通过 ELISA 测量上清液中 BDNF 的分泌，通过流式细胞术和 Transwell 测定分别检测 BDNF 中和抗体或 Trk 酪氨酸激酶抑制剂 K252a 对细胞凋亡和侵袭的影响。
在 HCC 标本中发现 BDNF（63.1%）或 TrkB（55.4%）的高表达，这与 HCC 的多发性和晚期显著相关。HCCLM3 中的 BDNF 分泌水平高于 HepG2 细胞。抗 BDNF 和 K252a 均可有效诱导 HepG2 和 HCCLM3 细胞凋亡并抑制侵袭。
这些发现表明 BDNF/TrkB 对 HCC 细胞的存活和侵袭至关重要。BDNF/TrkB 信号可能是预防 HCC 进展的有效靶点。
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