Anticancer effect of miR-124-loaded liposomal nanoparticles on pancreatic cancer progression

Abstract

Pancreatic cancer (PC) is a common malignancy that is characterized by strong invasiveness and rapid development. With lack of effective treatments, patients still suffer from poor outcome. In this study, we established liposomal nanoparticles carrying microRNA-124 (Ls/miR-124) and detected their inhibitory effect on PC cells. Ls/miR-124 nanoparticles were prepared and co-cultured with PC cells (Ls/miR-124 group), as some PC cells were treated with pure liposome particles (Ls group), or gemcitabine (gemcitabine group) and some untreated were treated as control group. Flow cytometry and transwell assay were used to determine apoptosis and migration of PC cells. Bax, Bcl-2, and Caspase-3 expressions were measured. The Ls/miR-124 nanoparticles presented around 100 nm size at 3:1 molar ratio of DOTAP/Chol, with stable properties and high potential. The fluorescence intensity of the cells in the Ls/miR-124 group and gemcitabine group were higher than Ls and blank groups. RT-qPCR analysis confirmed the up-regulation of miR-124 with high transfection efficiency of 85%. Proliferation of cells in each group increased upon culture. Administration of either Ls/miR-124 nanoparticles or gemcitabine significantly decreased PC cell proliferation and increased apoptosis at similar apoptotic rate of 29.76±3.78% and 30.15±3.57. Besides, the Ls/miR-124 and gemcitabine groups had cell cycle arrest in G0/G1 phase (67.98±3.45%) and exhibited decreased migration of 19.78±2.97% and invaded cells (42.56±6.98%). The expression of Bax in both groups decreased, while expressions of Bcl-2 and Caspase-3 increased. In conclusion, administration of Ls/miR-124 nanoparticles decreased cell viability and migration of PC cells, inhibiting cell cycle progression but increasing apoptosis and restraining development of PC.