The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, Soochow University, Suzhou 215123, China.
Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China.
Biochem Pharmacol. 2017 Sep 15;140:28-40. doi: 10.1016/j.bcp.2017.05.014. Epub 2017 May 20.
Pancreatic cancer (PC) is one of the most fatal cancers worldwide. The incidence and death rates are still increasing for PC. Curcumin is the biologically active diarylheptanoid constituent of the spice turmeric, which exerts its anticancer properties in various human cancers including PC. In particular, accumulating evidence has proved that curcumin targets numerous therapeutically important proteins in cell signaling pathways. The neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4) is an E3 HECT ubiquitin ligase and is frequently over-expressed in various cancers. It has reported that NEDD4 might facilitate tumorigenesis via targeting and degradation of multiple tumor suppressor proteins including PTEN. Hence, in the present study we explore whether curcumin inhibits NEDD4, resulting in the suppression of cell growth, migration and invasion in PC cells. We found that curcumin inhibited cell proliferation and triggered apoptosis in PC, which is associated with increased expression of PTEN and p73. These results suggested that inhibition of NEDD4 might be beneficial to the antitumor properties of curcumin on PC treatments.
胰腺癌（PC）是全球最致命的癌症之一。PC 的发病率和死亡率仍在上升。姜黄素是香料姜黄中的生物活性二芳基庚烷类成分，它在包括 PC 在内的各种人类癌症中发挥抗癌作用。特别是，越来越多的证据证明姜黄素靶向细胞信号通路中许多治疗上重要的蛋白质。神经前体细胞表达发育下调蛋白 4（NEDD4）是一种 E3 HECT 泛素连接酶，在各种癌症中经常过表达。有报道称，NEDD4 可能通过靶向和降解包括 PTEN 在内的多种肿瘤抑制蛋白促进肿瘤发生。因此，在本研究中，我们探讨了姜黄素是否抑制 NEDD4，从而抑制 PC 细胞的生长、迁移和侵袭。我们发现姜黄素抑制 PC 细胞增殖并触发细胞凋亡，这与 PTEN 和 p73 的表达增加有关。这些结果表明，抑制 NEDD4 可能有益于姜黄素在 PC 治疗中的抗肿瘤特性。
