Verteporfin suppresses cell survival, angiogenesis and vasculogenic mimicry of PDAC via disrupting the YAP-TEAD complex.

Verteporfin suppresses cell survival, angiogenesis and vasculogenic mimicry of PDAC via disrupting the YAP-TEAD complex.

Cancer Sci. 2016 Dec 21;:

Authors: Wei H, Wang F, Wang Y, Li T, Xiu P, Zhong J, Sun X, Li J

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. The Yes-associated protein-1 (YAP) plays a critical role in cell proliferation, apoptosis and angiogenesis. Verteporfin is a photosensitizer used in photodynamic therapy and also a small molecular inhibitor of the Hippo-YAP pathway. However, little is known whether verteporfin could inhibit YAP activity in PDAC cells. Our present results showed that verteporfin suppressed the proliferation of human PDAC PANC-1 and SW1990 cells by arresting cells at G1 phase, and inducing apoptosis in dose- and time-dependent manners. Verteporfin also inhibited the tumor growth on the PDAC xenograft model. Treatment with verteporfin led to downregulation of cyclinD1 and cyclinE1, modulation of Bcl-2 family proteins and activation of PARP. In addition, verteporfin exhibited an inhibitory effect on angiogenesis and vasculogenic mimicry via suppressing Ang2, MMP2, VE-cadherin, and α-SMA expression in vitro and in vivo. Mechanical studies demonstrated that verteporfin impaired YAP and TEAD interaction to suppress the expression of targeted genes. Our results provide a foundation for repurposing verteporfin as a promising anti-tumor drug in the treatment of pancreatic cancer by targeting the Hippo pathway. This article is protected by copyright. All rights reserved.

PMID: 28002618 [PubMed - as supplied by publisher]

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