Nasopharyngeal carcinoma (NPC) is a common malignant tumor and a major cause of mortality and morbidity in southern China. However, the mechanism is still elusive. Here, we focused on studying the role of squalene epoxidase (SQLE), a key enzyme of cholesterol biosynthesis, in the progression of NPC. Clinical study revealed that SQLE expression was significantly upregulated in NPC tissues compared to normal tissues from mRNA level and patients with high expression of SQLE showed a poor prognosis. In vitro experiments showed that SQLE overexpression led to a significant proliferation of cells whereas SQLE knockdown showed an opposite result. In vivo studies also showed that SQLE promoted tumor growth in nude mice. Further study revealed that SQLE promoted NPC proliferation by cholesteryl ester accumulation instead of cholesterol. Mechanism studies indicated that cholesteryl ester promoted NPC cell proliferation by activating the PI3K/AKT pathway and inhibition of this pathway in SQLE‐overexpressed or cholesteryl ester‐treated cells resulted in a significant reduction of NPC cell proliferation. These results indicate that the oncogenic effect of SQLE in NPC mainly resulted from cholesteryl ester accumulation and PI3K/AKT is a promising target for NPC with SQLE overexpression.

No abstract

The co-delivery of a drug and a target gene has become a primary strategy in cancer therapy. Based on our previous study, a synthesized star‑shaped co‑polymer consisting of β‑cyclodextrin (CD) and a poly(L‑lysine) dendron (PLLD) was used to co-deliver docetaxel (DOC) and matrix metalloproteinase 9 (MMP‑9) small interfering RNA, via CD‑PLLD/DOC/MMP‑9 complexes, into mice implanted with HNE‑1 human nasopharyngeal carcinoma (NPC) tumor cells in vivo. Unlike the commonly used amphiphilic co‑polymer micelles, the obtained CD derivative may be used directly for a combined delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vivo assays demonstrated that CD‑PLLD/DOC/MMP‑9 inhibited HNE‑1 tumor growth and decreased proliferating cell nuclear antigen expression levels, indicating a potential strategy for NPC therapy. In addition, the distribution of DOC and MMP‑9 was investigated; CD‑PLLD/DOC/MMP‑9 complexes were phagocytized in reticuloendothelial systems, including the liver and spleen, which requires further study. Furthermore, the complexes did not cross the blood‑brain barrier due to their large molecular size, suggesting they may be relatively safe. Additionally, the complexes mediated increased DOC concentrations with prolonged blood circulation and EGFP expression in HNE‑1 tumors. These results suggest the future potential application of CD-PLLD/DOC/MMP-9 for NPC therapy.

A novel folate (FA) receptor-targeted superparamagnetic Fe 3 O 4 nanoparticles (SPIONs) codelivering cisplatin (CDDP) and tissue factor pathway inhibitor-2 (TFPI-2) plasmid DNA (pDNA) was constructed. The core shell nanocomposites (FA-PEG-PEI@SPION-CDDP-TFPI-2) were composed of superparamagnetic Fe 3 O 4 core that binds CDDP and TFPI-2 shell that combines with folate-polyethylene glycol-polyethyleneimine (FA-PEG-PEI) via electrostatic interaction. The shell containing FA-PEG-PEI and TFPI-2 plasmid was synthesized through amidation reaction and electrostatic adsorption and the core containing SPION-CDDP was modified by aldehyde sodium alginate. Proton nuclear magnetic resonance and Fourier transform infrared spectra on FA-PEG-PEI polymers showed characteristic peaks of various metabolites in corresponding frequency. Transmission electron microscopy image of FA-PEG-PEI@SPION-CDDP-TFPI-2 nanoparticles demonstrated a near-monodisperse spherical morphology, while dynamic light scattering studies indicated an intensity-average diameter of 149.5 nm. Zeta potential was 14.89 ± 1.83 mv and the final concentration of loaded CDDP was 100 ug/ml. Gel electrophoresis data showed that the nanocomposite would protect TFPI-2 pDNA from being digested by DNases. Compared with CNE-2 cells, the good targetability and better gene transfection efficiency (57.9%) were detected by Prussian blue iron stain and fluorescence analysis in HNE-1 cells in vitro. The results suggested the potential application of FA-PEG-PEI@SPION-CDDP-TFPI-2 as a multifunctional anticancer nanomedicine on targeting therapy for FR positive NPC.