Lipid nanoparticles containing PlncRNA-1 promote apoptosis of liver cancer cells by down-regulating Wnt/beta-catenin signaling

Abstract

PlncRNA-1 has an anti-cancer property. Liposome nanoparticles (LNPs) are used as carriers of targeted drugs and contribute to tumor-targeted drug delivery. However, the interaction between LNPs containing PlncRNA-1 and β-catenin, a key component of Wnt signaling pathway, and its role in liver cancer have not yet been confirmed. Human liver cancer cells were exposed to LNPs containing PlncRNA-1 at different concentrations followed by analysis of cell proliferation, cell cycle distribution and apoptosis. Wnt/β-catenin pathway-related gene expression was determined. LNPs containing PlncRNA-1 dose-dependently suppressed the proliferation of liver cancer HepG2 cells with IC50 at 24 h, 48 h and 72 h of 12.8±0.67 μmol/L, 8.8±0.43 μmol/L and 4.6±0.42 μmol/L, respectively. PlncRNA-1-loaded LNPs (5, 10, and 20 μmol/L) dose-dependently arrested HepG2 cells in G2/M phase and induced apoptosis (p > 0.05). Administration of LNPs carrying PlncRNA-1 decreased the expression of overall, cytoplasmic, and nuclear β-catenin, thereby suppressing Wnt/β-catenin pathway. Protein expression levels of GSK-3 (p-tyr216) and Axin-2 were increased, while protein expression levels of Dvl-2, Dvl-3, GSK-3β, c-myc and survivin were significantly decreased. Invasion and metastasis of malignant tumors is an important factor. Inhibiting invasion of cancer cells effectively might improve the prognosis of cancer patients. LNPs carrying PlncRNA-1 promoted cell cycle transition and cell apoptosis by decreasing the expression of Dvl-2, Dvl-3, intracellular β-catenin, cytoplasmic β-catenin, and total β-catenin protein, which may relate to the inhibition of Wnt/β-catenin pathway.