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Verteporfin, a suppressor of YAP–TEAD complex, presents promising antitumor properties on ovarian cancer

Authors Feng J, Gou J, Jia J, Yi T, Cui T, Li Z

Received 6 April 2016

Accepted for publication 14 July 2016

Published 29 August 2016 Volume 2016:9 Pages 5371—5381


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati

Juntao Feng,1 Jinhai Gou,1 Jia Jia,1 Tao Yi,2 Tao Cui,1 Zhengyu Li1,2

1Department of Gynecology and Obstetrics, 2Sichuan Key Laboratory of Gynecologic Oncology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China

Abstract: Yes-associated protein (YAP) is a key transcriptional coactivator of Hippo pathway and has been shown to be an oncoprotein in ovarian cancer (OC). Verteporfin (VP), clinically used in photodynamic therapy for neovascular macular degeneration, has been recently proven to be a suppressor of YAP–TEAD complex and has shown potential in anticancer treatment. In this study, we aimed to explore the potential effect of VP in the treatment of OC. Our results showed that VP led to inhibition of proliferation in a time- and dose-dependent manner and to the suppression of migratory and invasive capacities of OC cells. Western blot and real-time polymerase chain reaction demonstrated that VP induced YAP cytoplasmic retention and deregulated inducible YAP and CCNs in OC cells. In vivo, VP exerted a significant effect on tumor growth in OVCAR8 xenograft mice, resulting in tumor nodules with lower average weight and reduced volume of gross ascites. In addition, VP treatment remarkably upregulated cytoplasmic YAP and phosphorylation YAP and downregulated CCN1 and CCN2, but exerted little effect on YAP-upstream components in Hippo pathway. In conclusion, our results suggested that VP may be a promising agent for OC, acting by suppressing YAP–TEAD complex.

Keywords: YAP, CCN2, ovarian cancer, verteporfin, Hippo pathway

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