The Anticancer Effects of Radachlorin-mediated Photodynamic Therapy in the Human Endometrial Adenocarcinoma Cell Line HEC-1-A

Anticancer Res. 2017 Nov;37(11):6251-6258. doi: 10.21873/anticanres.12076.

Abstract

Aim: We investigated the effect of photodynamic therapy (PDT) using radachlorin on invasion, vascular formation and apoptosis by targeting epidermal growth factor receptor (EGFR)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathways in the HEC-1-A endometrial adenocarcinoma cell line.

Materials and methods: To investigate the apoptotic pathway, we performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and western blot analysis. We also evaluated the effects of PDT on tubular capillary formation in and invasion by HEC-1-A cells with a tube formation assay, invasion assay, prostaglandin E2 (PGE2) assay, and western blot analysis.

Results: PDT had anticancer effects on HEC-1-A through activation of the intrinsic pathway of apoptosis via caspase-9 and poly-(ADP-ribose) polymerase (PARP). PDT also inhibited tubular capillary formation in and invasion by HEC-1-A under VEGF pretreatment, that resulted from down-regulation of VEGFR2, EGFR, Ras homolog gene family/ member A (RhoA) and PGE2. These results are indicative of the specificity of radachlorin-mediated PDT to VEGF.

Conclusion: The major advantage of radachlorin-mediated PDT is its selectivity for cancer tissue while maintaining adjacent normal endometrial tissue. Therefore, radachlorin-mediated PDT might offer high anticancer efficacy for endometrial adenocarcinoma and an especially useful modality for preserving fertility.

Keywords: EGFR; HEL-1-A; Radachlorin; apoptosis; endometrial adenocarcinoma cell line; photodynamic therapy.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Drug Combinations
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology*
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Light*
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology*
  • Porphyrins / pharmacology*
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Drug Combinations
  • Photosensitizing Agents
  • Porphyrins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • bremachlorin
  • EGFR protein, human
  • ErbB Receptors
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • rhoA GTP-Binding Protein