High Level Of Delta-Like Ligand 4 Suppresses The Metastasis Of Hepatocellular Carcinoma

This study aims to explore the role of Delta-like ligand 4 (DLL4) in human hepatocellular carcinoma (HCC), we examined the expression of DLL4 both in protein and ribonucleic acid levels. Additionally, the lentiviral vector over expression of DLL4 (Lv-DLL4-OE) was to assess the HCC cells biological behavior. 150 HCC tissues were detected by immunohistochemistry. Hepatocellular carcinoma, paracancer and normal liver samples were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). SMMC-7721 and HepG2 with Lv-DLL4-OE were investigated cells biological behavior by MTT and Transwell. In protein level, DLL4 expression in HCC was significantly different from paracancer tissues (P<0.05). DLL4 positive rate in HCC was 41.7% (61/150) and 81.3% (122/150) in paracancer tissues. The association of DLL4 with clinical parameters indicated that patients with low DLL4 protein levels were prone to metastasize (P<0.05). Kaplan-Meier analysis showed that patients with DLL4 positive expression was not statistically different with those negative in overall survival time (P>0.05). RT-PCR analysis showed DLL4 mRNA in tumor tissue was the lowest of three groups (P<0.05). The relationship between clinical features and DLL4 mRNA levels was consistent with protein levels except serum alpha fetal protein (AFP). Cell cultures confirmed that over expression DLL4 could significantly inhibit the migration capacity of HepG2 and SMMC-7721 (P<0.05), but did not affect cells proliferation. Our findings indicate that DLL4 was low express in HCC tissues, and over expression of DLL4 might suppress the migration ability in vitro. Therefore, DLL4 might be as a negative regulator involved in the development of HCC.