|
|
|
| Verteporfin synergizes the efficacy of anti-PD-1 in cholangiocarcinoma |
| Jianyang Fu a , Nicole A McGrath a , Jihye Lee a , Xin Wang a , Gagandeep Brar b , Changqing Xie a , ∗ |
a Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
b Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA
∗ Corresponding author.
E-mail address: changqing.xie@nih.gov (C. Xie). |
|
|
|
Abstract Background: Cholangiocarcinoma (CCA) is one of the primary hepatobiliary malignant neoplasms with only 10% of 5-year survival rate. Promising immunotherapy with the blockade of immune checkpoints has no clear benefit in CCA. The inhibition of YAP1 signaling by verteporfin has shown encouraging results by inhibiting cell proliferation and inducing apoptosis. This study aimed to evaluate the potential benefit of the combination of verteporfin and anti-programmed cell death 1 (PD-1) in CCA mouse model.
Methods: We assessed the cytotoxicity of verteporfin in human CCA cell lines in vitro, including both intrahepatic CCA and extrahepatic CCA cells. We examined the in vitro effect of verteporfin on cell proliferation, apoptosis, and stemness. We evaluated the in vivo efficacy of verteporfin, anti-PD-1, and a combination of both in subcutaneous CCA mouse model.
Results: Our study showed that verteporfin reduced tumor cell growth and enhanced apoptosis of human CCA tumor cells in vitro in a dose-dependent fashion. Nevertheless, verteporfin impaired stemness evidenced by reduced spheroid formation and colony formation, decreased numbers of cells with aldehyde dehydrogenase activity and positive cancer stem cell markers (all P < 0.05). The combination of verteporfin and anti-PD-1 reduced tumor burden in CCA subcutaneous SB1 tumor model compared to either agent alone.
Conclusions: Verteporfin exhibits antitumor effects in both intrahepatic and extrahepatic CCA cell lines and the combination with anti-PD-1 inhibited tumor growth.
|
|
|
|
|
|
|
|
|
2022, Vol. 21 
