Polyethylenimine 2k (PEI2k)/superparamagnetic iron oxide (SPIO) nanoparticle inhibits development of hepatocellular carcinoma through targeting of c-MET and Ets-1

Abstract

This study investigates the efficacy of N-Alkyl-polyethylenimine 2 kDa–stabilized superparamagnetic iron oxide ((PEI2k/SPIO) nanoparticles on hepatocellular carcinoma (HCC) in mice and explored the underlying mechanism. Highly metastatic HCC cells were cultured and mRNA expressions of c-MET and Ets-1 were determined by Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell viability was detected by CCK-8 and apoptosis was assessed by flow cytometry. After establishment of animal model for HCC, the rats were administered PEI2k/SPIO nanoparticles and/or Ets-1 inhibitor through tail vein. Cell apoptosis and proliferation were then assessed by EdU experiment and flow cytometry, and the levels of c-MET, Ets-1, MMP-2 were measured as well. HCC cells presented up-regulated c-MET and down-regulated Ets-1. Treatment with PEI2k/SPIO nanoparticles resulted in decreased in c-MET expression and increased Ets-1 in both cells and animals. The PEI2k/SPIO nanoparticles significantly decreased cell proliferation and suppressed tumor growth, and induced apoptosis. Besides, additional injection of Ets-1 enhanced phosphorylation activity of MMP-2 and alleviated PEI2k/SPIO’s effect on MMP-2 expression. Nanotechnology is known to improve delivery efficiency and hence affect prognosis. This study elucidated that, PEI2k/SPIO nanoparticles suppressed malignant characteristics of HCC cells and tumor growth through down-regulation of c-MET and growth factors and up-regulation of MMP-2 and Ets-1.