The combination of NVP-BEZ235 and rapamycin regulates nasopharyngeal carcinoma cell viability and apoptosis via the PI3K/AKT/mTOR pathway
The combination of NVP-BEZ235 and rapamycin regulates nasopharyngeal carcinoma cell viability and apoptosis via the PI3K/AKT/mTOR pathway
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DOI：
10.3892/etm.2018.6896
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发表时间：
2019-01-01
影响因子：
2.7
通讯作者：
Lin, Hong
中科院分区：
文献类型：
--
作者：
Luo, Hui;Yu, Yu-Yu;Lin, Hong
鼻咽癌是一种罕见的恶性肿瘤，具有显著的地理分布。关于NPC治疗，提高晚期患者的生存率似乎是有希望的。磷脂酰肌醇3-激酶（PI 3 K）/蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）通路失调与肿瘤发生密切相关。在本研究中，NPC细胞系SUNE 1被分为四组：对照组、NVP-BEZ 235组、雷帕霉素组和NVP-BEZ 235+雷帕霉素组。NVP-BEZ 235组中的SUNE 1细胞与NVP-BEZ 235一起孵育;雷帕霉素组中的细胞与雷帕霉素一起孵育，而NVP-BEZ 235+雷帕霉素组是指与NVP-BEZ 235和雷帕霉素的混合物一起孵育的SUNE 1细胞。对照组用相同量的溶剂处理。形态学、MTT、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记和流式细胞术分析表明，NVP-BEZ 235和雷帕霉素引起细胞形态学改变，抑制细胞活力并诱导细胞凋亡。逆转录-定量聚合酶链反应和蛋白质印迹显示NVP-BEZ 235和雷帕霉素的组合影响PI 3 K/AKT/mTOR通路的激活。NVP-BEZ 235和雷帕霉素的组合显著提高了药物治疗的效果。潜在的潜在机制可能包括抑制细胞活力、促进细胞凋亡和降低SUNE 1细胞中相对信号蛋白表达水平的联合作用。这些发现为NVP-BEZ 235抑制NPC发展提供了新的证据，并表明联合药物治疗（NVP-BEZ 235+雷帕霉素）在NPC临床治疗中具有潜在的应用前景。
Nasopharyngeal carcinoma (NPC) is a rare malignancy with a remarkable geographical distribution. Regarding NPC treatment, improving the survival rate of advanced patients seems promising. Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway deregulation is closely associated with tumorigenesis. In the present study, the NPC cell line SUNE1 was divided into four groups: Control, NVP-BEZ235, rapamycin, and NVP-BEZ235+rapamycin. SUNE1 cells in the NVP-BEZ235 group were incubated with NVP-BEZ235; cells in the rapamycin group were incubated with rapamycin, whereas the NVP-BEZ235+rapamycin group refers to SUNE1 cells incubated with a mixture of NVP-BEZ235 and rapamycin. The control group was treated with the same amount of vehicle. Morphological, MTT, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling and flow cytometry assays demonstrated that NVP-BEZ235 and rapamycin caused morphological changes, inhibited cell viability and induced cellular apoptosis. In addition, reverse transcription-quantitative polymerase chain reaction and western blot revealed that the combination of NVP-BEZ235 and rapamycin affected the activation of the PI3K/AKT/mTOR pathway. The combination of NVP-BEZ235 and rapamycin significantly improved the effect of the drug therapy. The potential underlying mechanism may comprise the joint effects of inhibiting cell viability, promoting cellular apoptosis and reducing relative signal protein expression levels in SUNE1 cells. These findings provided novel evidence that NVP-BEZ235 suppresses NPC development, and indicated a promising potential application of combination drug therapy (NVP-BEZ235+rapamycin) for the clinical treatment of NPC.