A novel anti-cancer effect of atelocollagen-conjugated miR-520d-5p on pancreatic cancer cells in vitro and in a mouse xenograft model

Abstract

Background:We have previously shown that hsa-miR-520d-5p can convert undifferentiated hepatoma cells into the status of pluripotent stem cells or mesenchymal stem cells (MSCs) via a demethylation process and P53 upregulation in vivo. Here, we examined anti-cancer effect of miR-520d-5p on three human pancreatic cancer (PC) cells. Material and methods:After generating GFP-expressing cancer cells, we transfected 520d-5p into three PC cell lines (KLM-1, PK-45p or PK-9) to examine the key gene expression and the change of malignant properties. Also, we examined the therapeutic effect of 520d-5p on KLM-1 using atelocollagen-conjugated miR-520d-5p (520d/atelocollagen).Results: Tumor growth was suppressed by more than 80% each week by 520d/atelocollagen, compared with scramble/atelocollagen (scram./.atelocollagen) or atelocollagen alone. Interestingly, 520d-5p induced PK-9 cells to the transformation accompanied by apoptosis, resulting in the benignant transformation like pancreatic acinar cells with the functions of secreting pancreatic enzyme (lipase or amylase) without malignant properties.Conclusions: This is the first reports that we confirmed an anti-cancer effect of 520d/atelocollagen or the benignant conversion on PC cells in vivo study. The development to optimize this carrier for drug delivery system (DDS) is expected to elevate the efficiency to enter each tumor cell and provide for the miRNA medicine as a novel therapeutic modality.