Suksawat Manida, Techasen Anchalee, Namwat Nisana, Boonsong Thianrut, Titapun Attapol, Ungarreevittaya Piti, Yongvanit Puangrat, Loilome Watcharin
Department of Biochemistry Faculty of Medicine Khon Kaen University Thailand.
Cholangiocarcinoma Research Institute Khon Kaen University Thailand.
FEBS Open Bio. 2018 Mar 2;8(4):513-522. doi: 10.1002/2211-5463.12388. eCollection 2018 Apr.
The isoform of nitric oxide synthase (NOS) found in endothelial cells (eNOS) plays a crucial role in vasodilation. We recently reported the activation of eNOS in cholangiocarcinoma (CCA) tissues and cell lines. Moreover, we also reported that the abundance of eNOS and phosphorylated eNOS (p-eNOS), as well as its upstream regulator proteins, is significantly associated with the metastatic status of CCA patients. However, the function of eNOS in CCA progression has not been addressed. Therefore, the present study aimed to investigate the function of eNOS involved in the migration and invasion ability of CCA cell lines. The results reveal that eNOS activation significantly increases migration and invasion ability of CCA cells the up-regulation of phosphorylated vasodilator-stimulated protein (p-VASP). A combination treatment with recombinant human vascular endothelial growth factor C and eNOS inhibitor (-nitro-l-arginine methyl ester hydrochloride) resulted in the down-regulation of p-VASP, as well as a decreased migration and invasion ability of the CCA cell line. Thus, this work suggests that eNOS can serve as an attractive target to inhibit the progression of CCA.
在内皮细胞中发现的一氧化氮合酶（NOS）同工型（eNOS）在血管舒张中起关键作用。我们最近报道了胆管癌（CCA）组织和细胞系中eNOS的激活。此外，我们还报道了eNOS和磷酸化eNOS（p-eNOS）的丰度及其上游调节蛋白与CCA患者的转移状态显著相关。然而，eNOS在CCA进展中的功能尚未得到研究。因此，本研究旨在探讨eNOS在CCA细胞系迁移和侵袭能力中的作用。结果显示，eNOS激活显著增加了CCA细胞的迁移和侵袭能力，这与磷酸化血管舒张刺激蛋白（p-VASP）的上调有关。重组人血管内皮生长因子C和eNOS抑制剂（盐酸L-硝基精氨酸甲酯）联合处理导致p-VASP下调，以及CCA细胞系迁移和侵袭能力降低。因此，这项研究表明eNOS可作为抑制CCA进展的一个有吸引力的靶点。
