In vivo synergistic anti-tumor effect of paclitaxel nanoparticles combined with radiotherapy on human cervical carcinoma

Drug Deliv. 2017 Nov;24(1):75-82. doi: 10.1080/10717544.2016.1230902.

Abstract

In this study, our purpose was to explore the synergistic anti-tumor effect and mechanism of paclitaxel nanoparticles (PTX-NPs) combined with radiotherapy (RT) on human cervical carcinoma (HeLa). PTX-NPs were prepared by a solid dispersion method using methoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL), which combined with RT exerted a potent and high efficient effect against cervical cancer. In vivo antitumor activity of PTX-NPs combined with RT, was estimated using nude mice carrying Hela cell xenograft tumor. The results were evaluated using microfluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) and immunohistochemistry. The results showed that PTX-NPs possessed a more efficient effect than PTX when combined with RT (p < 0.05). PTX-NPs in combination with RT might inhibit cell proliferation through its action on Ki-67, and decreased micro-vessel density (MVD) associated with CD31 and vascular endothelial growth factor (VEGF). These results suggested that PTX-NPs possessed a synergistic anti-tumor effect against cervical cancer when combined with RT.

Keywords: Paclitaxel; cervical cancer; nanoparticle; radiotherapy; synergistic effect.

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / chemistry
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Cell Proliferation / drug effects
  • Chemoradiotherapy*
  • Drug Carriers*
  • Drug Compounding
  • Female
  • Fluorodeoxyglucose F18
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanomedicine
  • Nanoparticles*
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*
  • Positron Emission Tomography Computed Tomography
  • Radiopharmaceuticals
  • Technology, Pharmaceutical / methods
  • Time Factors
  • Uterine Cervical Neoplasms / diagnostic imaging
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy*
  • Vascular Endothelial Growth Factor A / metabolism
  • X-Ray Microtomography
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Ki-67 Antigen
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Polyesters
  • Radiopharmaceuticals
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • methoxy poly(ethylene glycol-co-epsilon-caprolactone)
  • Fluorodeoxyglucose F18
  • Polyethylene Glycols
  • Paclitaxel