Capecitabine metronomic chemotherapy inhibits the proliferation of gastric cancer cells through anti-angiogenesis

Oncol Rep. 2015 Apr;33(4):1753-62. doi: 10.3892/or.2015.3765. Epub 2015 Jan 29.

Abstract

To evaluate the inhibitory effect and mechanism of capecitabine metronomic chemotherapy on gastric cancer cells. In vitro, the effects of 5-fluorouracil (Fu) metronomic chemotherapy on proliferation, apoptosis, tube formation ability, and angiogenesis were detected. In vivo, Ki-67, CD34 and VEGF were detected by immunohistochemical staining (IHC). Flow cytometry was used to detect the percentage of circulating endothelial progenitors (CEPs), and VEGF and PDGF were detected by ELISA in the peripheral blood of nude mice. The proliferation of the SGC-7901 and AGS gastric cancer cell lines in the metronomic 5-Fu group was decreased compared with the control group in vitro. The total length of the small tubes and tubular junction numbers were significantly lower in the metronomic group than the control group. The VEGF and PDGF levels in the cell culture supernatants were lower in the metronomic group than the control group. Compared with the control group, the CEP percentage was decreased in the peripheral blood of tumor-bearing nude mice following treatment with metronomic 5-Fu or capecitabine chemotherapy. No significant changes were found in the conventional or control group. In the peripheral blood of tumor-bearing nude mice, the VEGF and PDGF levels were decreased in the metronomic groups. Metronomic 5-Fu inhibited the proliferation of gastric cancer cells in vitro and in vivo, and their antitumor effects were non-inferior to those of conventional dose chemotherapy, with mild side effects. Thus, tumor inhibition may be attributed to anti-angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / blood supply
  • Adenocarcinoma / pathology*
  • Administration, Metronomic
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / pharmacology*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Biomarkers, Tumor
  • Blood Cell Count
  • Capecitabine / administration & dosage
  • Capecitabine / pharmacology*
  • Capecitabine / therapeutic use
  • Cell Line, Tumor
  • Culture Media
  • Drug Screening Assays, Antitumor
  • Endothelial Progenitor Cells / drug effects
  • Fluorouracil / administration & dosage
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Morphogenesis / drug effects
  • Platelet-Derived Growth Factor / analysis
  • Sincalide / analysis
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / blood supply
  • Stomach Neoplasms / pathology*
  • Vascular Endothelial Growth Factor A / analysis
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Culture Media
  • Platelet-Derived Growth Factor
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Capecitabine
  • Sincalide
  • Fluorouracil