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

Virginie Cerec; Fausto Andreola; Stephen P. Pereira

doi:10.1117/12.828411

13 July 2009 Effect of verteporfin-PDT on the Notch signaling pathway in cholangiocarcinoma (CCA) cell lines

Virginie Cerec, Fausto Andreola, Stephen P. Pereira

Proceedings Volume 7380, Photodynamic Therapy: Back to the Future; 73806J (2009) https://doi.org/10.1117/12.828411
Event: 12th World Congress of the International Photodynamic Association, 2009, Seattle, Washington, United States

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.

Citation Download Citation

Virginie Cerec, Fausto Andreola, and Stephen P. Pereira "Effect of verteporfin-PDT on the Notch signaling pathway in cholangiocarcinoma (CCA) cell lines", Proc. SPIE 7380, Photodynamic Therapy: Back to the Future, 73806J (13 July 2009); https://doi.org/10.1117/12.828411

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