The circadian clock gene PER2 enhances chemotherapeutic efficacy in nasopharyngeal carcinoma when combined with a targeted nanosystem
The circadian clock gene PER2 enhances chemotherapeutic efficacy in nasopharyngeal carcinoma when combined with a targeted nanosystem
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生物钟基因PER2与靶向纳米系统相结合可增强鼻咽癌的化疗效果
DOI：
10.1039/d0tb00595a
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发表时间：
2020-06-28
影响因子：
7
通讯作者：
Xia, Hechun
中科院分区：
文献类型：
--
作者：
Hou, Li;Li, Hailiang;Xia, Hechun
40%以上的晚期鼻咽癌（NPC）患者因放化疗耐药而导致治疗失败，包括局部复发和远处转移。生物钟基因被鉴定为以时间依赖性方式调节癌症进展和化学放射敏感性。一种新的纳米系统可以确保化疗剂在设定的时间在肿瘤部位的积累和可控释放。在这项研究中，我们研究了生物钟基因的表达，并确定周期性昼夜节律调节因子2（PER 2）作为肿瘤抑制因子在NPC进展中起着关键作用。无标记蛋白质组学方法显示PER 2过表达可抑制ERK/MAPK通路。在NPC中评估PER 2过表达与包含叶酸（FA）、与虎红共价偶联的上转换纳米颗粒的纳米系统一起的化疗效果。（UCNPs-RB）、10-羟基喜树碱（HCPT）和脂质-全氟己烷（PFH）（FURH-PFH-NPs）. PER 2过表达与纳米药物的靶向和控释相结合提高了NPC中的化疗功效，对肿瘤的时间治疗具有潜在的应用价值。
Treatment failure occurs in more than 40% of advanced nasopharyngeal carcinoma (NPC) patients including local recurrence and distant metastasis due to chemoradioresistance. Circadian clock genes were identified as regulating cancer progression and chemoradiosensitivity in a time-dependent manner. A novel nanosystem can ensure the accumulation and controllable release of chemotherapeutic agents at the tumour site at a set time. In this study, we investigated the expression of circadian clock genes and identified that period circadian regulator 2 (PER2) as a tumour suppressor plays a key role in NPC progression. A label-free proteomic approach showed thatPER2overexpression can inhibit the ERK/MAPK pathway. The chemotherapeutic effect ofPER2overexpression was assessed in NPC together with the nanosystem comprising folic acid (FA), upconverting nanoparticles covalently coupled with Rose Bengal (UCNPs-RB), 10-hydroxycamptothecin (HCPT) and lipid-perfluorohexane (PFH) (FURH-PFH-NPs).PER2overexpression combined with the targeted and controlled release of nanoagents elevated chemotherapeutic efficacy in NPC, which has potential application value for the chronotherapy of tumours.