Objective: To investigate the expression of brain-derived neurotrophic factor ( BDNF ) and its primary receptor, tropo-mysin-related kinase B ( TrkB ) in hepatocellular carcinoma ( HCC ) tissues, and to evaluate the functions of these proteins in the onco-genesis and progression of HCC. Methods: The expression of BDNF and TrkB in 65 HCC cases was evaluated via immunohistochemi-cal staining. In the human HCC HepG2 cell lines, the secretory BDNF in the supernatant liquid was measured using enzyme-linked im-munosorbent 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.%目的:研究BDNF及其受体TrkB在人肝细胞癌(HCC)中的表达,并探讨二者在HCC发生、发展中的作用.方法:采用免疫组织化学方法检测BDNF和TrkB在65例HCC组织中的表达.在人HCC细胞系HepG2中,采用ELISA方法检测BDNF在培养上清中的分泌水平,分别采用流式细胞术和Transwell细胞侵袭方法测定BDNF中和抗体或TrkB激酶活性抑制剂K252a处理对细胞凋亡和侵袭的影响.结果:65例HCC组织标本中,41例(63.1%)高表达BDNF,36例(55.4%)TrkB阳性表达,而且BDNF高表达于多发性HCC(P<0.01),TrkB阳性率在多发性HCC中较高(P<0.05).此外,BDNF高表达和TrkB阳性均与晚期HCC显著相关(P 均<0.05).BDNF在HepG2细胞培养上清中的浓度为(88.56±7.45)pg/mL.BDNF抗体或K252a均可有效诱导HepG2细胞凋亡,并抑制细胞侵袭.结论:BDNF/TrkB可能对HCC细胞的存活和侵袭具有重要的支持作用,并促进HCC的发展演进.
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