Killing tumor cells: the effect of photodynamic therapy using mono-L-aspartyl chlorine and NS-398.
BACKGROUND
Photodynamic therapy (PDT) is a useful treatment for malignant tumors. PDT involves the administration of a photosensitive drug that is selected by neoplastic tissues and their vasculature. One such photosensitizer is mono-l-aspartyl chlorine e6 (NPe6). Recent evidence suggests that the presence of the cyclooxygenase-2 (COX-2) inhibitor NS-398 may potentiate the effect of photosensitizing agents. This study was designed to determine if the addition of NS-398 to NPe6-induced PDT in single or fractionated dosing would result in greater tumor kill.


METHODS
Colon-38 tumor was subcutaneously implanted into both flanks of mice and allowed to grow to 0.5 to 1.0 cm. Mice were randomly allocated to 5 groups: (1) single dose of NPe6; (2) fractionated dose of NPe6; (3) NS-398 only; (4) single dose of NPe6 + NS-398; and (5) fractionated dose of NPe6 + NS-398. The left flank was shielded from exposure to irradiation. Tumor size was measured before initiation of PDT and at the time of sacrifice.


RESULTS
The initial tumor weights of both flanks were not significantly different between all groups. Tumor weights at the time of death after PDT using NPe6 were significantly less than their paired tumors in the untreated flanks (P <0.0001). Tumor weights in the treated flanks were significantly less in the group receiving the fractionated dosing of NPe6 as compared to the single dose of NPe6 (P = 0.0037). NS-398 plus the single dose of NPe6 significantly decreased tumor weight in the PDT-treated flank (P = 0.035) at a level equivalent to that observed with fractionated dosing of the photosensitizer in the absence of NS-398. NS-398 did not significantly further decrease tumor weight in the group that received the fractionated dose of NPe6.


CONCLUSIONS
Fractionated dosing of NPe6 demonstrated the best tumor kill. However, NS-398 did not potentiate the effect of PDT using fractionated dosing of NPe6. While PDT using the single NPe6 dose significantly decreased tumor weight, the addition of NS-398 potentiated the killing effect.
Harvey
Elizabeth H
EH
Department of Surgery, Wayne State University School of Medicine, 6C-UHC, 4201 St. Antoine, Detroit, MI 48201, USA.
Webber
John
J
Kessel
David
D
Fromm
David
D
D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D009578:Nitrobenzenes / Q000008:administration & dosage* / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D011166:Porphyrins / Q000008:administration & dosage* / Q000494:pharmacology; D013449:Sulfonamides / Q000008:administration & dosage* / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D017319:Photosensitizing Agents; D011166:Porphyrins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C053434:Talaporfin