Invasion and metastasis are the main causes leading to the death of patients with hepatocellular carcinoma (HCC). Multivesicular liposomes loaded with oleanolic acid (OA-MVLs) have been well demonstrated to suppress survival, growth and angiogenesis of HCC cells. Emerging evidence demonstrates that OA was able to suppress the invasion of HCC cells by down-regulating myocyte enhancer factor-2. We hypothesized that the optimized OA-MVLs could inhibit the migration and invasion of HCC cells. In this study, we utilized central composite design and response surface methodology to assess the influence of some parameters on particle size and encapsulation efficiency and obtain the optimized formulation of OA-MVLs. Subsequently, the human HCC cell lines SMMC-7721 and HepG2 were treated with different doses of OA-MVLs and OA, respectively. Cellular survival, adhesion, migration and invasion in vitro were evaluated. We found that the optimized OA-MVLs significantly decreased the ability of HCC cells to adhere, migrate and invade in vitro. Furthermore, OA-MVLs significantly inhibited the survival of HCC cells at 160 µmol/L but showed no obvious inhibition effect on the cell vitality of normal liver cells. Our findings indicate that OA-MVLs did inhibit the cell survival, adhesion, invasion and metastasis of HCC cells in vitro. Although the involved mechanisms are still unclear, our findings can contribute to a better development of a preventive and therapeutic strategy for human HCC.
Keywords: adhesion; central composite design; invasion; migration; multivesicular liposomes; oleanolic acid.