Z Gastroenterol 2014; 52 - P39
DOI: 10.1055/s-0034-1376023

MicroRNA expression and photodynamic therapy in biliary tract cancer cell lines

A Wagner 1, C Mayr 1, D Bach 1, R Illig 2, K Plaetzer 3, F Berr 1, M Pichler 4, D Neureiter 2, T Kiesslich 1, 5
  • 1Department of Internal Medicine I, Paracelsus Medical University, Salzburg, Austria
  • 2Institute of Pathology, Paracelsus Medical University, Salzburg, Austria
  • 3Division of Physics and Biophysics, Department of Materials Science and Physics, University of Salzburg, Salzburg, Austria
  • 4Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria
  • 5Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria

Photodynamic therapy (PDT) is established for palliative treatment of non-resectable hBTC showing a considerable benefit for survival and quality of life with few side effects. Currently, the factors determining the cellular response of biliary tract cancer cells towards PDT are unknown. Due to their multifaceted functions in cellular signaling, microRNAs (miRNAs) are a promising analyte to investigate the mechanisms governing sensitivity and resistance.

For two photosensitizers, Photofrin® and Foscan®, the cellular sensitivity towards in vitro PDT was investigated in eight BTC cell lines using the resazurin viability test. Each cell line (untreated) was profiled for expression of n = 754 miRNAs using the TaqMan® Array Human MicroRNA A+B Cards. Statistical analysis was used to identify miRNAs associated with PDT efficiency. Furthermore correlation analysis of miR expression and markers of proliferation and differentiation (Ck19, Ck8/18a, vimentin, cyclin D1 and E-cadherin) was performed.

PDT was particularly effective in cells with high levels of clustered miRs 25 – 106b and (in case of miR-106b) a phenotype characterized by high expression of the mesenchymal marker vimentin and high proliferation (cyclinD1 and Ki67 expression). A PDT-resistant phenotype was characterized by high expression of miR-200 family members and (in case of miR-cluster 200a/b-429) expression of differentiation markers Ck19 and Ck8/18a. Bioinformatic analysis of predicted and validated downstream targets suggests direct involvement of miRs-200c and -203 in response mechanisms to oxidative stress, nitric oxide biosynthesis and in stress-activated pathway signaling cascades.

The heterogeneity in the PDT response is associated with a distinct miRNome pattern providing a novel tool for predicting the efficiency of PDT. Following confirmation by subsequent mechanistic approaches, this information may allow optimization of the PDT protocol to develop more reliable and efficient treatment regimens.