Combination of Vitamin K2 and Phosphatidylcholine Inhibits Hepatocarcinogenesis via Mir-16 Regulating

Aim: Vitamin K2 and phosphatidylcholine are two common drugs in clinical treatment. Studies carried out in the past several years demonstrated vitamin K2 and phosphatidylcholine could separately inhibit hepatocarcinogenesis. In this study, we sought to investigate the synergy of vitamin K2 and phosphatidylcholine and the potential mechanism. Methods: Multiple assays were performed to evaluate the effect of combination administration in vitro and in vivo. Then microRNA microarray, bioinformatics analysis and western blot were performed to explore the potential mechanism of drug action. Results: In vitro, combined administration of vitamin K2 and phosphatidylcholine for 72 hours showed significant anti-tumor effect in four HCC cell lines (Hep-3B, Hep-G2, Huh-7 and SMMC-7721). In vivo, tumor growth was significantly suppressed in the treated group. According to microRNA microarray and bioinformatics analysis, miR-16 was significantly up-regulated and WNT signaling pathway was strongly correlated with the process of anti-tumor. Then western blot analysis indicated that low-expression of WNT3A, p-β-catenin and Bcl-2 accorded with the assumption of miR-16’s function. Conclusions: At last we inferred, given together, vitamin K2 and phosphatidylcholine exhibited synergy against hepatocarcinogenesis via miR-16 regulating. However, further study is needed to confirm these regulatory relationships.