Comparative study of FosPeg® photodynamic effect on nasopharyngeal carcinoma cells in 2D and 3D models

J Photochem Photobiol B. 2020 Sep:210:111987. doi: 10.1016/j.jphotobiol.2020.111987. Epub 2020 Aug 7.

Abstract

Photodynamic Therapy (PDT) offers an alternative option for the treatment of nasopharyngeal carcinoma (NPC). The utilization of 3-dimensional (3D) culture model might provide better understanding of PDT effects on NPC cells. The aim of this in vitro study was to compare PDT effect on NPC cells using 2D and 3D models. Two 3D culture models were established using liquid overlay method with agarose base (MCL) and hanging drop method (MCS). PDT was carried out using the combination of FosPeg® and 652 nm laser in 3D and conventional 2D models. The effects of 3D culture size and morphology on the uptake and distribution of sensitizer and gene expression were examined. Photocytotoxity, mode of cell death, and protein expression were compared for 2D and 3D models. Regular and irregular NPC spheroids were obtained from MCL and MCS methods, respectively. A significantly down-regulation of LMP1 mRNA were observed in MCL spheroid. The sensitizer uptake in 3D spheroids was half of 2D culture. More sensitizers were required to obtain IC50 in 3D spheroids. Apoptosis, necrosis and autophagosomes were detected in PDT treated 2D and 3D cells. Different protein expression patterns were observed in 2D and 3D models. FosPeg® PDT is effective in killing NPC cells. MCL-derived 3D spheroid model is more suitable for the evaluation of PDT killing mechanisms.

Keywords: 2D monolayer cells; 3D spheroids; NPC; PDT.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • Apoptosis / drug effects
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Gene Expression Regulation / drug effects*
  • Humans
  • Light
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Nasopharyngeal Carcinoma / drug therapy
  • Nasopharyngeal Carcinoma / metabolism
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Photochemotherapy
  • Photosensitizing Agents / pharmacology*
  • Photosensitizing Agents / therapeutic use
  • Spheroids, Cellular / drug effects*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Neoplasm Proteins
  • Photosensitizing Agents
  • Matrix Metalloproteinase 2