쥐 종양 모델에서 Chlorine e6 매개 광역학 치료

Abstract

Photodynamic therapy (PDT) is a clinically approved and rapidly developing cancer treatment regimen. It is a minimally invasive procedure that requires the administration of a photosensitizer followed by the illumination of the tumor with light of an appropriate wavelength. In the presence of molecular oxygen, cytotoxic intermediaries are produced, thus damaging cellular structures containing the photosensitizer. In the present study, the author examined the effectiveness of newly develped chlorin e6-induced PDT on malignant animal tumor model of Sprague-Dawley (SD) rat. Three-week-old male SD rats were inoculated s.c. on the right flank with our previously established k-ras-transformed RK3E cell line (RK3E-ras, RK3E-ras-Fluc, total, 2.5x107 cells). The experiments were carried out 1 week after inoculation of tumor cells, by which time the tumors had reached about 0.7 mm to 1.0 cm in diameter. LS-chlorin e6 (LS Pharm Co., Gwangju, Korea) was administrated intravenously by the tail vein of SD rat at a dosage of 10 mg/kg after inhalation anesthesia of ether. Twenty-four hours after LS-chlorin e6 administration, PDT was performed using a laser diode (Geumgwang Co., Ltd., Daejeon, Korea) at a light dose of 100 J/cm2 and wavelength of 664 nm. Animals were monitered daily and tumor volume was measured by caliper. The tumor treated with PDT using Ce6 had significant reduction in tumor size examined by gross tumor volume, softex x-ray image, molecular imaging analysis, respectively. PCNA immunostaining and TUNEL assay revealed that the treated tumor caused significant inhibition of tumor formation with decreased tumor cell proliferation and increased apoptosis. Clusterin expression was increased in the PDT treated tumor, whereas VEGF expression was decreased in the PDT treated tumor. These data showed Ce6-induced PDT effectively arrested the tumor growth by inhibiting cell proliferation, angiogenesis, and inducing apoptosis. These findings provide the potential value of Ce6-induced PDT as an alternative candidate for anti-tumor therapy. Further biochemical and cellular studies will reveal the precise molecular mechanism of cell death induced by PDT.