Hematoporphyrin derivative-mediated photodynamic therapy inhibits tumor growth in human cholangiocarcinoma in vitro and in vivo

Abstract

Aim: To investigate the effects of hematoporphyrin derivative-mediated photodynamic therapy (HPD-PDT) on cell growth in human cholangiocarcinoma in vitro and in vivo, as well as the underlying mechanisms of these effects. Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate growth status of human cholangiocarcinoma cell line (QBC939). Hoechst 33258 staining and flow cytometry assays were applied to determine cell apoptosis. Western blotting analysis was performed to detect the release of cytochrome c in QBC939 cells, and caspases enzymatic assay was used to investigate the activation of caspase-3, -8, and -9. Further, tumor growth after subcutaneous implantation of QBC939 cells in nude mice was monitored. Results: HPD-PDT inhibits QBC939 cell growth via cell apoptosis in vitro, and initiates cell mitochondria apoptosis pathway by the release of cytochrome c and the activation of caspase-9 and -3. Moreover, HPD-PDT also inhibits subcutaneous tumor growth of QBC939 cells and reduces tumor cell mitosis in nude mice. Conclusion: HPD-PDT inhibits tumor growth of human cholangiocarcinoma, suggesting that HPD-PDT is useful in cholangiocarcinoma therapy. © 2009 The Japan Society of Hepatology.