Photodynamic therapy of human lung cancer xenografts in mice.
BACKGROUND
There is a need to develop novel therapies for non-small cell lung cancer (NSCLC). Photodynamic therapy has been used successfully for endobronchial palliation of NSCLC, and its role in early stages of disease is being explored. We hypothesized that a novel photosensitizer, PS1, would be more effective than the standard agent, porfimer sodium (Photofrin or PFII), in treating human lung cancer xenografts in mice.


METHODS
Patient-derived NSCLC xenografts were established subcutaneously in severe combined immune deficiency mice. Two groups of five mice were injected with PS1 (3-[1'-m-iodobenzyloxy]ethyl-3-devinylpyropheophorbide-a), a chlorophyll-a derivative, or PFII (a purified version of hematoporphyrin derivative) and then treated with nonthermal laser light. Four mice were treated with laser light without photosensitizer and six mice received no treatment at all. All mice were then observed for tumor growth. The tumor growth end point, time-to-1000 mm(3), was evaluated using standard Kaplan-Meier methods and the log-rank test. Tumor hematoxylin and eosin and caspase 3 staining was done to evaluate necrosis and apoptosis.


RESULTS
The median time-to-1000 mm(3) was 12, 12, 26, and 52 d for the control, light only, PFII, and PS1 groups. There was a significant association between the tumor growth end point and treatment (P < 0.05). Hematoxylin and eosin staining revealed <1%, 0%, 67%, and 80% necrosis, and caspase 3 positivity was 2%, <1%, 17%, and 39%, respectively, in the same four groups.


CONCLUSIONS
The mice treated with PS1 exhibited a longer time for tumor regrowth and showed more tumor necrosis and apoptosis compared with the other treatment groups. Thus, the novel photosensitizer, PS1, was demonstrated to be more effective than porfimer sodium in this preclinical pilot study.
Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York; Department of Surgery, State University of New York at Buffalo, University at Buffalo, Buffalo, New York. Electronic address: chumy.nwogu@roswellpark.org.
Chukwumere
C
Nwogu
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York.
Paula
P
Pera
Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York.
Wiam
W
Bshara
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York.
Kristopher
K
Attwood
Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York.
Ravindra
R
Pandey
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017323:Dihematoporphyrin Ether / Q000627:therapeutic use*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D010865:Pilot Projects; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D017319:Photosensitizing Agents; C505556:methyl 3-(1'-3-iodobenzyloxyethyl)-3-devinylpyropheophorbide-a; D002734:Chlorophyll; D017323:Dihematoporphyrin Ether
Apoptosis; Lung cancer; Photodynamic therapy; Tumor necrosis