Uptake and phototoxicity of meso-tetrahydroxyphenyl chlorine are highly variable in human biliary tract cancer cell lines and correlate with markers of differentiation and proliferation

作者：Kiesslich Tobias; Neureiter Daniel; Alinger Beate; Jansky Gerhard L; Berlanda Juergen; Mkrtchyan Vahagn; Ocker Matthias; Plaetzer Kristjan; Berr Frieder^*

来源：Photochemical and Photobiological Sciences, 2010, 9(5): 734-743.

DOI：10.1039/b9pp00201d

Photodynamic therapy (PDT) using Photofrin (R) and, recently, Foscan (R) has gained broad acceptance for palliative treatment of non- resectable cholangiocarcinoma (CC). No information, however, is available whether the phenotype of CC tumour cells has an effect on the ef. ciency of the treatment. Using a well-characterised set of n = 9 biliary tract cancer cell lines this study investigated the uptake, phototoxicity, and release of meso-tetrahydroxyphenyl chlorine (mTHPC, Foscan (R)) after incubation with 200 or 400 ng ml(-1) mTHPC. For uptake of mTHPC we found great variations between the individual cell lines (up to a factor 2), resulting in even more pronounced differences in phototoxicity. Based on statistical classi. cation by hierarchical cluster analysis, two groups of cell lines can be distinguished which are characterised by either high or low susceptibility towards mTHPC- based photodynamic treatment. Correlation analysis with previously established immunochemical parameters showed that cells with a low cytokeratin-19 (ductal differentiation), high vimentin (mesenchymal marker), and high proliferative phenotype preferentially show higher uptake of mTHPC and subsequent phototoxicity. These results demonstrate high variability of biliary tract cancer cells when subjected to mTHPC- based photodynamic treatment and identify possible markers that could be used in the clinical setting in order to predict the ef. ciency of PDT and adjust the dose for complete tumour elimination.

• 出版日期2010