Studies have shown that inactivation of Trk by tyrosine kinase inhibitors was correlated with more apoptotic [30], or less invasive tumor cells [31], and aiming at interfering TrkB activation might be helpful in the development of effective anticancer therapies. K252a is a selective inhibitor of the tyrosine protein kinase activity of the trk family of oncogenes and neurotrophin receptors [32]. In this study, apoptotic cells were

observed increasing after K252a treatment, which was considered that TrkB activated by BDNF was participated in the survival of HepG2 and HCCLM3 cells. Moreover, K252a used in this study also demonstrated a critical role of TrkB kinase activity in BDNF-induced invasion of HepG2 and HCCLM3 cells. Further investigations check details should be carried out for the detailed signalings downstream of BDNF/TrkB in regulating the survival and invasion of HCC cells. Taken together, our study confirmed that both BDNF and TrkB were higher expressed in multiple HCCs, which was positively correlated with tumor progression. Secretory BDNF in supernatant of HCCLM3 cells with high metastatic potential were much

more than that in HepG2 cells. Furthermore, HepG2 and HCCLM3 cells treated with BDNF neutralizing antibody or Trk tyrosine kinase inhibitor K252a showed increased apoptosis and decreased invasion. Our data thus revealed an important role of BDNF/TrkB in regulating survival and invasion of HCC cells and probably provided new insight into the inhibition of BDNF/TrkB signaling see more as a target of anti-HCC therapies. Nevertheless, the signaling pathway(s) downstream

of BDNF/TrkB that involved in metastasis of HCC required further studies. Conclusions Our data suggested that BDNF/TrkB supports the survival of HCC cells, and seems to serve as a critical 4-Aminobutyrate aminotransferase mediator in the progression of intrahepatic dissemination of HCC cells, and prevention of BDNF/TrkB signaling could be an effective way in HCC therapy. Acknowledgements and Funding We are very grateful to Dr. Siyang Zhang for technical help and writing assistance. This work was supported by grants from the Project Sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (the Project-sponsored by SRF for ROCS, SEM) of China (2008890), and The Educational Department of Liaoning Province, China (2008824). Electronic supplementary AZD4547 material Additional file 1: Clinicopathological characteristics of 65 HCC patients in detail. Distribution, differentiation, stage and lymph node metastasis were included, as well as BDNF score and TrkB expression by immunohistochemistry in HCC specimens, which were statistically analyzed in Table 1 and Table 2. (DOC 154 KB) References 1. Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J: Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer 2000, 89:500–507.PubMedCrossRef 2.