A comparison of susceptibility to photodynamic treatment between endothelial and tumor cells in vitro and in vivo

Summary 

Background

Photodynamic therapy (PDT) is being widely used for treatment of cancer and non-malignant diseases. The mechanisms of phototoxicity to solid tumor are not yet completely understood. Knowledge of the inherent sensitivity of endothelial cells in comparison to tumor cells would be helpful to predict tumor response to PDT, and thereby optimize treatment protocols.

Methods and results

The intrinsic sensitivity of rodent endothelial and tumor cells to PDT was studied using an in vitro clonogenicity assay that strictly controlled for light and photosensitizer exposure, as well as cellular photosensitizer and oxygen concentration. Taking into consideration cell size, ploidy and glutathione content, no significant difference in sensitivity to phototoxicity was observed between tumor and endothelial cells. Electron microscopy studies were also conducted to examine endothelial and tumor cells for differential cellular damage following interstitial PDT of rat prostate tumor. No evidence for selective damage to endothelial cells was demonstrated.

Conclusions

Rodent tumor cells and endothelial cells are equally susceptible to Photofrin-mediated PDT damage. Sufficient photosensitizer accumulated in solid tumor seems to be one of the key factors for PDT effectiveness.

Abbreviations: BME, Eagles basal media, DMSO, dimethylsulfoxide, EMT-6, mouse mammary tumor cells, FCS, fetal calf serum, HpD, hematoporphyrin derivative, MEM, minimal essential media, PBS, phosphate buffered saline solution, PDT, photodynamic therapy, Photofrin or PII, porfimer sodium, R3327-AT, rat prostate tumor (anaplastic), SDS, sodium dodecyl sulphate, UNA-ME, mouse endothelial cells

Keywords: Endothelial cells, Photodynamic therapy (PDT), Photofrin, Prostate tumor