Verteporfin, a suppressor of YAP-TEAD complex, presents promising antitumor properties on ovarian cancer.
Verteporfin, a suppressor of YAP-TEAD complex, presents promising antitumor properties on ovarian cancer.
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DOI：
10.2147/ott.s109979
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发表时间：
2016
影响因子：
4
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Feng J;Gou J;Jia J;Yi T;Cui T;Li Z
Yes相关蛋白（雅普）是Hippo通路的关键转录辅激活因子，是卵巢癌（OC）中的一种癌蛋白。维替泊芬（Verteporfin，VP）是近年来发现的一种YAP-TEAD复合物抑制剂，在光动力学疗法治疗新生血管性黄斑变性中有重要应用价值。本研究旨在探讨VP在治疗OC中的潜在作用。我们的研究结果表明，VP导致抑制增殖的时间和剂量依赖性的方式和抑制OC细胞的迁移和侵袭能力。Western blot和实时荧光定量聚合酶链反应结果显示VP诱导OC细胞内雅普滞留，并使诱导型雅普和CCN表达下调。在体内，VP对OVCAR 8异种移植小鼠的肿瘤生长产生显著影响，导致肿瘤结节的平均重量降低，总腹水体积减少。此外，VP处理显著上调胞浆雅普和磷酸化雅普，下调CCN 1和CCN 2，但对Hippo通路中YAP上游组分影响不大。总之，我们的研究结果表明，VP可能是一个有前途的代理OC，通过抑制YAP-TEAD复合物。
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.