SPHK1 inhibitor suppresses cell proliferation and invasion associated with the inhibition of NF-κB pathway in hepatocellular carcinoma

• DOI: 10.1007/s13277-014-2665-7
• Publication Date: 2014-12-23T08:10:02Z
• Authors: Zijie Zhang; Zhenyu Yan; Zheng Yuan; Yanzhen Sun; Haifa He; Chunyang Mai
• Keywords: Sphingosine kinase 1; Viability assay

Sphingosine kinase 1 (SphK1) is an oncogenic enzyme promoting transformation, proliferation, and angiogenesis of a number human tumors. However, its effect on hepatocellular carcinoma (HCC) behavior has not been fully clarified. The purpose this study was to determine the correlation between HCC SphK1, evaluate SphK1 inhibitor N,N-dimethylsphingosine (DMS) in HCC. expression measured tissue samples from 76 paired adjacent noncancerous liver tissues (NT) by immunohistochemistry, quantitative real-time PCR, Western blotting analysis. DMS tested cells evaluating cell viability vitro. Transwell migration invasion assay were carried out for functional Furthermore, analysis performed examine impact PI3K/Akt/NF-kB signaling. High Sphk1 observed 84.21% (64/76) versus 15.79% (12/76) non-tumorous tissues; difference statistically significant (P < 0.001). results confirmed blot analyses PCR. inhibited proliferation SK-Hep1 MHCCLM3 which have relatively high level time- concentration-dependent manner, distinctly suppressed after undergoing treatment with DMS. markedly phosphorylations Akt NF-κB cells. Our data suggest that pathogenesis maybe mediated Sphk1, specific can play therapeutic role thus, could represent selective targets molecularly targeted treatments