Enhanced antitumor efficacy using epirubicin and schisandrin B co-delivery liposomes modified with PFV via inhibiting tumor metastasis

Drug Dev Ind Pharm. 2020 Apr;46(4):621-634. doi: 10.1080/03639045.2020.1742145. Epub 2020 Mar 25.

Abstract

As a malignant tumor, breast cancer is very prone to metastasis. Chemotherapy is one of the most common means for treating breast cancer. However, due to the serious metastasis and the poor targeting effect of traditional chemotherapeutic drugs, even after years of efforts, the therapeutic effect is still unsatisfied. Therefore, in this study, we constructed a kind of PFV modified epirubicin plus schisandrin B liposomes to solve the above disadvantages. In vitro experiments showed that the targeting liposomes with ideal physicochemical property could increase the cytotoxicity of MDA-MB-435S cells, destroy the formation of vasculogenic mimicry (VM), and inhibit tumor invasion and migration. Action mechanisms indicated that the inhibition of targeting liposomes on tumor metastasis was attributed to the regulation of the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), vimentin (VIM), and E-cadherin (E-cad). In vivo pharmacodynamic experiments showed that the targeting liposomes could significantly improve the antitumor effect in mice. H&E staining and TUNEL results showed that the targeting liposomes could promote the apoptosis of tumor cells. Hence, the PFV modified epirubicin plus schisandrin B liposomes constructed in this study provided a new therapeutic strategy for breast cancer.

Keywords: PFV; epirubicin; liposomes; schisandrin B; tumor metastasis.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Chick Embryo
  • Chorioallantoic Membrane
  • Cyclooctanes / administration & dosage
  • Epirubicin / administration & dosage*
  • Female
  • Humans
  • Lignans / administration & dosage*
  • Liposomes
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Mice
  • Neoplasm Invasiveness
  • Polycyclic Compounds / administration & dosage*
  • Xenograft Model Antitumor Assays

Substances

  • Cyclooctanes
  • Lignans
  • Liposomes
  • Polycyclic Compounds
  • schizandrin B
  • Epirubicin