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Proceedings Paper

Effect of verteporfin-PDT on the Notch signaling pathway in cholangiocarcinoma (CCA) cell lines
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Paper Abstract

Accumulating preclinical and clinical evidence supports a pro-oncogenic function for Notch signaling in several solid tumors. Therefore, Notch inhibitory agents, such as gamma-secretase inhibitors (GSI), are being investigated as cancer therapeutic agents and a potential adjuvant to conventional chemo/radiotherapy. To date, no in vitro data are available on the cellular response and effect of either photodynamic therapy (PDT) or GSI on human cholangiocarcinoma (CCA). Consequently, we aimed to study the: (i) constitutive expression of Notch signaling pathway in CCA cell lines; (ii) response to Verteporfin-PDT and to GSI, as single agents on CCA cell lines; (iii) effect of Verteporfin-PDT on Notch signaling pathway expression. Expression of Notch signaling components was studied in two cholangiocarcinoma cell lines, HuCCT1 and TFK-1 (intra- and extrahepatic, respectively). No difference in basal expression of Notch1, 2 and Jagged1 was observed in either cell line. In contrast, Notch3 was found to be weakly and highly expressed in HuCCT1 and TFK-1 cells, respectively - supporting our recent microarray data which showed Notch3 overexpression in biliary brushings from patients with extrahepatic CCA. HuCCT1 and TFK-1 differentially responded to Verteporfin-PDT treatment; preliminary data showed no clear effect of GSI on proliferation/apoptosis in either cell line following short exposure (6 and 24h). Following Verteporfin-PDT, Notch1, 2 and Jagged-1 expression was down-regulated in both cell lines, while Notch3 expression was unaffected in HuCCT1 cells and down-regulated in TFK-1 cells. The Notch signaling pathway could represent a potential target for combination therapy in CCA treatment.

Paper Details

Date Published: 13 July 2009
PDF: 7 pages
Proc. SPIE 7380, Photodynamic Therapy: Back to the Future, 73806J (13 July 2009); doi: 10.1117/12.828411
Show Author Affiliations
Virginie Cerec, Univ. College London (United Kingdom)
Fausto Andreola, Univ. College London (United Kingdom)
Stephen P. Pereira, Univ. College London (United Kingdom)

Published in SPIE Proceedings Vol. 7380:
Photodynamic Therapy: Back to the Future
David H. Kessel, Editor(s)

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