[1]万婕,祝琳,雷越,等.FoxM1通过Wnt/β-catenin信号通路对鼻咽癌细胞5-8F增殖、迁移的影响[J].第三军医大学学报,2018,40(05):380-386.
 WAN Jie,ZHU Lin,LEI Yue,et al.Effect of siRNA mediated FoxM1 silencing on proliferation and migration of nasopharyngeal carcinoma 58F cells via Wnt/β-catenin signaling pathway[J].J Third Mil Med Univ,2018,40(05):380-386.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第05期
页码:
380-386
栏目:
基础医学
出版日期:
2018-03-15

文章信息/Info

Title:
Effect of siRNA mediated FoxM1 silencing on proliferation and migration of nasopharyngeal carcinoma  58F cells via Wnt/β-catenin signaling pathway
作者:
万婕祝琳雷越刘亚男文韬宇李丹丹叶琳陈鸿雁
重庆医科大学附属第一医院:耳鼻喉科,胸心外科;西南医科大学附属医院耳鼻咽喉头颈外科
Author(s):
WAN Jie ZHU Lin LEI Yue LIU Yanan WEN Taoyu LI Dandan YE Lin CHEN Hongyan

Department of Otolaryngology, Department of Cardiothoracic Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016; Department of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, China

关键词:
鼻咽癌FoxM1Wnt/&beta-catenin信号通路细胞增殖细胞迁移
Keywords:
nasopharyngeal carcinoma FoxM1 Wnt/&beta-catenin signaling pathway proliferation migration
分类号:
R394.3; R730.23; R739.63
文献标志码:
A
摘要:

目的     探讨FoxM1对鼻咽癌细胞5-8F恶性生物学行为的影响及其可能机制。方法    将化学合成的靶向FoxM1的siRNA转染鼻咽癌细胞5-8F(FoxM1-siRNA组),并设立空白对照组、阴性对照组,采用RT-PCR及Western blot检测FoxM1表达变化。采用MTT法、FCM法、Transwell法分别检测下调FoxM1表达对细胞增殖、周期、凋亡、迁移的影响。Western blot检测下调FoxM1表达后β-catenin、C-Myc、Cyclin D1、MMP-2、MMP-9蛋白表达变化。结果     转染FoxM1-siRNA的5-8F细胞FoxM1 mRNA和蛋白表达水平降低(P<0.05)。下调FoxM1表达可抑制5-8F细胞增殖(P<0.05),FoxM1-siRNA组的凋亡率为(22.68±0.67)%,较阴性对照组[(11.74±1.36)%]和空白对照组[(10.94±1.52)%]显著增加(P<0.05),细胞周期阻滞于G0/G1期。FoxM1-siRNA组细胞穿膜数(100.00±10.97)明显低于阴性对照组(246.00±6.66)和空白对照组(233.70±12.41),细胞迁移能力降低(P<0.05)。下调FoxM1的表达可抑制β-catenin细胞核表达,抑制C-Myc、Cyclin D1、MMP-2、MMP-9总蛋白表达(P<0.001)。结论    FoxM1表达下调抑制鼻咽癌细胞5-8F的增殖,诱导细胞凋亡,降低细胞迁移能力,使细胞周期阻滞于G0/G1期。其机制可能是通过抑制Wnt通路关键蛋白β-catenin细胞核表达从而抑制Wnt通路活性实现的。

Abstract:

Objective    To investigate the effect of siRNA mediated FoxM1 silencing on malignant behaviors of nasopharyngeal carcinoma cell line 5-8F via Wnt/β-catenin signaling pathway. Methods    The FoxM1-siRNA by chemical synthesis was transfected into 5-8F cells, and the blank and negative control cells were set up. Real-time PCR (RT-PCR) and Western blotting were used to detect the mRNA and protein levels of FoxM1 respectively. MTT assay, flow cytometry and Transwell chamber test were used to determine the effect of FoxM1 on proliferation, apoptosis, cell cycle distribution and migration of 5-8F cells. The protein expression levels of β-catenin, C-Myc, Cyclin D1, MMP-2 and MMP-9 were detected by Western blotting. Results    The mRNA and protein levels of FoxM1 were decreased obviously after FoxM1-siRNA transfection in 5-8F cells (P<0.05). When compared with the blank and negative control cells, the silence also inhibited the proliferation (P<0.05), but enhanced apoptotic rate [(22.68±0.67)% vs (10.94±1.52)% and (11.74±1.36)%, P<0.05], arrested the cell cycle at G0/G1 phase, and decreased the number of invaded cells (100.00±10.97 vs 233.70±12.41 and 246.00±6.66) and cell migration ability (P<0.05). Furthermore, Western blotting demonstrated that the nuclear protein level of β-catenin and the total protein levels of C-Myc, Cyclin D1, MMP-2 and MMP-9 were decreased after FoxM1-siRNA transfection (P<0.05). Conclusion     siRNA mediated FoxM1 silencing increases the apoptotic rate, inhibits the proliferation, reduces the migration, and arrests cell cycle at G0/G1 phase in nasopharyngeal carcinoma 5-8F cells. Its mechanism may be through suppressing the expression of  β-catenin, key protein of Wnt signaling pathway, and thus inhibiting the activation of the pathway.

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更新日期/Last Update: 2018-03-10