Curcumol inhibits EBV-positive Nasopharyngeal carcinoma migration and invasion by targeting nucleolin
Curcumol inhibits EBV-positive Nasopharyngeal carcinoma migration and invasion by targeting nucleolin
复制标题
姜黄酚通过靶向核仁素抑制 EBV 阳性鼻咽癌的迁移和侵袭。
DOI：
10.1016/j.bcp.2021.114742
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发表时间：
2021-09-14
影响因子：
5.8
通讯作者：
Chen, Xu
中科院分区：
文献类型：
--
作者：
Guan, Xiao;Yu, Dan;Chen, Xu
转移是EBV阳性鼻咽癌（NPC）患者复发和死亡的主要原因。以往的报道表明，莪术醇具有抗癌和抗病毒作用，但很少有文献系统地阐述莪术醇在EBV阳性肿瘤中的作用机制。本实验中，我们发现莪术醇在CNE 2细胞中的靶蛋白是nucelolin（NCL），而NCL在促进C666-1细胞的迁移和侵袭中起重要作用，并发现NCL的表达决定了莪术醇的疗效水平。NCL与EB病毒核抗原1（EBNA 1）相互作用，激活VEGFA/VEGFR 1/PI 3 K/AKT信号通路，促进鼻咽癌细胞的侵袭和转移。进一步的研究表明，NCL的差异表达和莪术醇的干预仅对VEGFR 1在细胞核内的积聚具有调节作用，从而加强了莪术醇通过NCL介导的抗癌作用。本研究结果提示，莪术醇通过下调EBNA 1和靶向NCL抑制VEGFA/VEGFR 1/PI 3 K/AKT信号通路发挥抗EBV阳性NPC侵袭转移作用，为莪术醇临床应用于治疗EBV阳性NPC提供了新的药理学依据
Metastasis is a major cause of recurrence and death in patients with EBV-positive Nasopharyngeal carcinoma (NPC). Previous reports documented that curcumol has both anti-cancer and anti-viral effects, but there is little literature systematically addressing the mechanism of curcumol in EBV-positive tumors. Previously we found that nucelolin (NCL) is a target protein of curcumol in CNE2 cells, an EBV-negative NPC, and in this experiment, we reported a critical role for NCL in promoting migration and invasion of C666-1 cells, an EBV-positive NPC, and found that the expression of NCL determined the level of curcumol's efficacy. Mechanistically, NCL interacted with Epstein-Barr Virus Nuclear Antigen 1 (EBNA1) to activate VEGFA/VEGFR1/PI3K/AKT signaling pathway, which in turn promoted NPC cell invasion and metastasis. Moreover, further study showed that the differential expression of NCL and curcumol intervention only had a regulatory effect on the nuclear accumulation of VEGFR1, which strengthened the anti-cancer effect of curcumol mediated through NCL. Our findings indicated that curcumol exerted anti EBV-positive NPC invasion and metastasis by downregulating EBNA1 and inhibiting VEGFA/VEGFR1/PI3K/AKT signaling by targeting NCL, which provides a novel pharmacological basis for curcumol's clinical use in treating patients with EBV-positive NPC