Photodynamic Therapy Using Novel Glucose-conjugated Chlorin Increases Apoptosis of Cholangiocellular Carcinoma in Comparison with Talaporfin Sodium.

Photodynamic therapy (PDT) is an effective laser treatment for locally treating advanced bile duct carcinoma (BDC). The study's objective was to evaluate the increased cytocidal effect by apoptotic PDT using a novel photosensitizer, glucose-conjugated chlorin, by irradiation of light-emitting diode laser (G-PDT) in comparison with conventional PDT using talaporfin sodium (T-PDT).The cytocidal effect of G-PDT was compared to that of T-PDT as a control. Tumor viability was determined by an in vitro MTS assay. The percentage of apoptosis-positive cells was examined by triple stain flow cytometry (annexin V, ethidium homodimer III and Hoechst 33342) in the BDC cell line (NOZ cell) in vitro. The change in transplanted tumor volume in vivo (4-week-old male BALB/c mice) was examined 7 days after PDT.Cell death was induced in a light dose-dependent manner by PDT. The laser power was set at 5 Jules/cm(2) to obtain half maximal inhibitory concentration (IC50) in T-PDT and G-PDT and the concentration of photosensitivity for G-PDT (2.02 μg/ml) was lower than that for T-PDT (4.14 μg/ml). Both T-PDT and G-PDT showed increased induction rates in comparison to the light only or G-chlorin only. Furthermore, the rate of apoptosis in the G-PDT (92.6%) was increased in comparison to that in the T-PDT (38.9%). The increased rates of tumor volume during the 7 days in both the G-PDT and T-PDT groups were significantly lower than that in the non-PDT group (p<0.01). At day 7, the increased rates of tumor volume in the G-PDT group were significantly lower than that in the T-PDT group (p<0.05).The new G-PDT treatment showed a high prevalence of apoptosis and inhibition of tumor growth in treatment of BDC cells.