Fe3O4-solamargine induces apoptosis and inhibits metastasis of pancreatic cancer cells

Int J Oncol. 2019 Mar;54(3):905-915. doi: 10.3892/ijo.2018.4637. Epub 2018 Nov 19.

Abstract

Fe3O4-magnetic liposome (MLP) can deliver drugs to target tissues and can increase drug efficacy. The present study aimed to investigate the effects of solamargine (SM) and Fe3O4-SM in pancreatic cancer (PC). Cell viability was detected using a Cell Counting kit‑8 assay. Apoptosis and cell cycle progression was tested using a flow cytometry assay. A scratch assay was used to examine cell metastasis. Quantitative polymerase chain reaction, western blot analysis or immunohistochemical analysis were performed to determine the expression of target factors. Magnetic resonance imagining (MRI) and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling were conducted to detect tumor growth and apoptosis in vivo, respectively. It was demonstrated that Fe3O4-SM inhibited cancer cell growth via a slow release of SM over an extended period of time. SM was revealed to induce apoptosis and cell cycle arrest. Furthermore, SM decreased the expression of X-linked inhibitor of apoptosis, Survivin, Ki‑67, proliferating cell nuclear antigen and cyclin D1, but increased the activity of caspase-3. It was also observed that SM inhibited tumor cell metastasis by modulating the expression of matrix metalloproteinase (MMP)-2 and TIMP metallopeptidase inhibitor-2. Furthermore, the phosphorylation of protein kinase B and mechanistic target of rapamycin was suppressed by SM. Notably, the effect of SM was enhanced by Fe3O4-SM. The malignant growth of PC was decreased by SM in vivo. Furthermore, the expression of Ki‑67 was decreased by SM and Fe3O4-SM. Additionally, cell apoptosis was increased in the Fe3O4-SM group, compared with the SM group. The present study illustrated the antitumor effect and action mec-hanism produced by SM. Additionally, it was demonstrated that Fe3O4-SM was more effective than SM in protecting against PC.

Keywords: solamargine; Fe3O4-solamargine; magnetic resonance imaging; pancreatic cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Biomarkers, Tumor / genetics
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Drug Delivery Systems
  • Ferrosoferric Oxide / chemistry
  • Ferrosoferric Oxide / pharmacokinetics
  • Ferrosoferric Oxide / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liposomes / chemistry
  • Male
  • Mice
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Signal Transduction / drug effects
  • Solanaceous Alkaloids / chemistry
  • Solanaceous Alkaloids / pharmacokinetics
  • Solanaceous Alkaloids / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Liposomes
  • Solanaceous Alkaloids
  • beta-solamarine
  • Ferrosoferric Oxide