Preclinical Study of Antineoplastic Sinoporphyrin Sodium-PDT via In Vitro and In Vivo Models

Molecules. 2017 Jan 11;22(1):112. doi: 10.3390/molecules22010112.

Abstract

Photodynamic therapy (PDT) investigations have seen stable increases and the development of new photosensitizers is a heated topic. Sinoporphyrin sodium is a new photosensitizer isolated from Photofrin. This article evaluated its anticancer effects by clonogenic assays, MTT assays and xenograft experiments in comparison to Photofrin. The clonogenicity inhibition rates of sinoporphyrin sodium-PDT towards four human cancer cell lines ranged from 85.5% to 94.2% at 0.5 μg/mL under 630 nm irradiation of 30 mW/cm² for 180 s. For MTT assays, the IC50 ranges of Photofrin-PDT and sinoporphyrin sodium-PDT towards human cancer cells were 0.3 μg/mL to 5.5 μg/mL and 0.1 μg/mL to 0.8 μg/mL under the same irradiation conditions, respectively. The IC50 values of Photofrin-PDT and sinoporphyrin sodium-PDT towards human skin cells, HaCaT, were 10 μg/mL and 1.0 μg/mL, respectively. Esophagus carcinoma and hepatoma xenograft models were established to evaluate the in vivo antineoplastic efficacy. A control group, Photofrin-PDT group (20 mg/kg) and sinoporphyrin sodium group at three doses, 0.5 mg/kg, 1 mg/kg and 2 mg/kg, were set. Mice were injected with photosensitizers 24 h before 60 J 630 nm laser irradiation. The tumor weight inhibition ratio of 2 mg/kg sinoporphyrin sodium-PDT reached approximately 90%. Besides, the tumor growths were significantly slowed down by 2 mg/kg sinoporphyrin sodium-PDT, which was equivalent to 20 mg/kg Photofrin-PDT. In sum, sinoporphyrin sodium-PDT showed great anticancer efficacy and with a smaller dose compared with Photofrin. Further investigations are warranted.

Keywords: MTT assay; clonogenic assay; photodynamic therapy; sinoporphyrin sodium; xenografts model.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Dihematoporphyrin Ether / chemistry
  • Drug Evaluation, Preclinical
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Lasers, Excimer
  • Light
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Photochemotherapy / methods*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / isolation & purification
  • Photosensitizing Agents / pharmacology*
  • Porphyrins / chemistry
  • Porphyrins / isolation & purification
  • Porphyrins / pharmacology*
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Photosensitizing Agents
  • Porphyrins
  • sinoporphyrin sodium
  • Dihematoporphyrin Ether