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新城疫病毒D90株在口腔鳞状细胞癌中的抗肿瘤活性

Antineoplastic activity of Newcastle disease virus strain D90 in oral squamous cell carcinoma.

作者信息

Zhang Chun-Xiao, Ye Long-Wei, Liu Ying, Xu Xiao-Ya, Li Dan-Rui, Yang Yan-Qing, Sun Lu-Lu, Yuan Jie

机构信息

Department of Oral Health Sciences, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.

出版信息

Tumour Biol. 2015 Sep;36(9):7121-31. doi: 10.1007/s13277-015-3433-z. Epub 2015 Apr 16.

Abstract

Newcastle disease virus (NDV), an avian paramyxovirus, possesses the ability to kill tumor cells. Here, we report the effects of NDV strain D90, which was isolated in China, against oral squamous cell carcinoma (OSCC) cells. In this study, we showed that the cell death induced by D90 was apoptotic. Furthermore, the apoptosis induced by D90 was dependent on the mitochondrial pathway, and the death receptor pathway may be not involved. Bax and Bcl-2 also played a role in the apoptosis induced by D90. Lymph node metastasis is a serious problem for oral cancer; we therefore evaluated the impact of D90 on the migration and invasion of OSCC cells. NDV D90 affected microtubules and microfilaments to inhibit the motility of OSCC prior to apoptosis. The effects of D90 on the migration and invasion rates of OSCC cells were evaluated by migration and invasion assays. Subsequently, the changes in sp1, RECK, MMP-2, and MMP-9 induced by a low concentration of D90 were detected by western blot and gelatin zymography. D90 significantly inhibited the invasion and metastasis of OSCC cells by decreasing the expression of sp1 and increasing the expression of RECK to suppress the expression and activity of MMP-2 and MMP-9.

摘要

新城疫病毒(NDV)是一种禽副粘病毒,具有杀死肿瘤细胞的能力。在此,我们报告了在中国分离得到的NDV毒株D90对口腔鳞状细胞癌(OSCC)细胞的作用。在本研究中,我们表明D90诱导的细胞死亡是凋亡性的。此外,D90诱导的凋亡依赖于线粒体途径,可能不涉及死亡受体途径。Bax和Bcl-2在D90诱导的凋亡中也发挥了作用。淋巴结转移是口腔癌的一个严重问题;因此,我们评估了D90对OSCC细胞迁移和侵袭的影响。NDV D90在凋亡前影响微管和微丝以抑制OSCC的运动性。通过迁移和侵袭试验评估D90对OSCC细胞迁移和侵袭率的影响。随后,通过蛋白质免疫印迹法和明胶酶谱法检测低浓度D90诱导的sp1、RECK、MMP-2和MMP-9的变化。D90通过降低sp1的表达和增加RECK的表达来抑制MMP-2和MMP-9的表达和活性,从而显著抑制OSCC细胞的侵袭和转移。

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