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.