Inhibition of cancer cell migration with CuS@ mSiO2-PEG nanoparticles by repressing MMP-2/MMP-9 expression

Int J Nanomedicine. 2017 Dec 21:13:103-116. doi: 10.2147/IJN.S148487. eCollection 2018.

Abstract

The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study. Using CuS@mSiO2-PEG NP stimulation and a transwell migration assay, we found that the migration of HeLa cells was significantly decreased. This phenomenon may be associated with two classical proteins in metastasis: matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9). In addition, the mechanism may closely associate with non-receptor tyrosine kinase protein (SRC)/focal adhesion kinase (FAK) signaling pathway which varies in vivo and in vitro. To confirm the differences in the expression of SRC and FAK, related inhibitors were studied for additional comparison. Also, the results indicated that even though the migration inhibition was closely related to SRC and FAK signaling pathway, there may be another unknown regulation mechanism existing and its metastasis inhibition was significant. Confirmed by long-term survival curve study, CuS@mSiO2-PEG NPs significantly reduced the metastasis of cancer cells and improved the survival rates of metastasis in a mouse model. Thus, we believe that the direct influence of NPs on cancer cell metastasis is a promising study topic.

Keywords: MMPs; SRC/FAK signaling pathway; metastasis inhibition; photothermal nanoparticles; survival curves.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Copper / pharmacology*
  • Focal Adhesion Kinase 1 / metabolism
  • HeLa Cells
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Polyethylene Glycols / chemistry
  • Signal Transduction / drug effects
  • Silicon Dioxide / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Polyethylene Glycols
  • Silicon Dioxide
  • Copper
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • cupric sulfide