In Vivo and In Vitro Effects of ATM/ATR Signaling Pathway on Proliferation, Apoptosis, and Radiosensitivity of Nasopharyngeal Carcinoma Cells

2017 ◽  
Vol 32 (6) ◽  
pp. 193-203 ◽  
Author(s):  
Ming Wang ◽  
Gang Liu ◽  
Guo-Ping Shan ◽  
Bing-Bing Wang
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Carcinoma Cells ◽  
In Vitro Effects

Chk1 inhibitor Gö6976 enhances the sensitivity of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy in vitro and in vivo

2010 ◽  
Vol 297 (2) ◽  
pp. 190-197 ◽  
Author(s):  
Zizhen Feng ◽  
Shuangbing Xu ◽  
Mengzhong Liu ◽  
Yi-Xin Zeng ◽  
Tiebang Kang
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Carcinoma Cells ◽  
Chk1 Inhibitor

scholarly journals RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Ying-Ying Liang ◽  
Xu-Bin Deng ◽  
Xian-Tao Lin ◽  
Li-Li Jiang ◽  
Xiao-Ting Huang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Underlying Mechanism ◽  
Carcinoma Cells ◽  
Dependent Manner ◽  
Transcriptional Coactivator ◽  
Actin Remodeling ◽  
Aggressive Tumor ◽  
Subunit B

Abstract Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor characterized by distant metastasis. Deletion or down-regulation of the tumor suppressor protein ras-association domain family protein1 isoform A (RASSF1A) has been confirmed to be a key event in NPC progression; however, little is known about the effects or underlying mechanism of RASSF1A on the malignant phenotype. In the present study, we observed that RASSF1A expression inhibited the malignant phenotypes of NPC cells. Stable silencing of RASSF1A in NPC cell lines induced self-renewal properties and tumorigenicity in vivo/in vitro and the acquisition of an invasive phenotype in vitro. Mechanistically, RASSF1A inactivated Yes-associated Protein 1 (YAP1), a transcriptional coactivator, through actin remodeling, which further contributed to Platelet Derived Growth Factor Subunit B (PDGFB) transcription inhibition. Treatment with ectopic PDGFB partially increased the malignancy of NPC cells with transient knockdown of YAP1. Collectively, these findings suggest that RASSF1A inhibits malignant phenotypes by repressing PDGFB expression in a YAP1-dependent manner. PDGFB may serve as a potential interest of therapeutic regulators in patients with metastatic NPC.

scholarly journals EBV encoded miRNA BART8-3p promotes radioresistance in nasopharyngeal carcinoma by regulating ATM/ATR signaling pathway

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Xiaohan Zhou ◽  
Jialing Zheng ◽  
Ying Tang ◽  
Yanling lin ◽  
Lingzhi Wang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Signaling Pathway ◽  
Ataxia Telangiectasia ◽  
Molecular Mechanisms ◽  
Radiation Treatment ◽  
Ataxia Telangiectasia Mutated ◽  
Barr Virus ◽  
Radiotherapy Resistance

Abstract Resistance to radiotherapy is one of the main causes of treatment failure in patients with nasopharyngeal carcinoma (NPC). Epstein-Barr virus (EBV) infection is an important factor in the pathogenesis of NPC, and EBV-encoded microRNAs (miRNAs) promote NPC progression. However, the role of EBV-encoded miRNAs in the radiosensitivity of NPC remains unclear. Here, we investigated the effects of EBV-miR-BART8-3p on radiotherapy resistance in NPC cells in vitro and in vivo, and explored the underlying molecular mechanisms. Inhibitors of ataxia telangiectasia mutated (ATM)/ataxia telangiectasia mutated and Rad3-related (ATR) (KU60019 and AZD6738, respectively) were used to examine radiotherapy resistance. We proved that EBV-miR-BART8-3p promoted NPC cell proliferation in response to irradiation in vitro and associated with the induction of cell cycle arrest at the G2/M phase, which was a positive factor for the DNA repair after radiation treatment. Besides, EBV-miR-BART8-3p could increase the size of xenograft tumors significantly in nude mice. Treatment with KU60019 or AZD6738 increased the radiosensitivity of NPC by suppressing the expression of p-ATM and p-ATR. The present results indicate that EBV-miR-BART8-3p promotes radioresistance in NPC by modulating the activity of ATM/ATR signaling pathway.

scholarly journals Antitumor and Radiosensitization Effects of a CXCR2 Inhibitor in Nasopharyngeal Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaobei Liu ◽  
Tianxia Lan ◽  
Fei Mo ◽  
Jingyun Yang ◽  
Yuquan Wei ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Carcinoma Cells ◽  
Carcinoma Cell Lines ◽  
Damage Repair ◽  
Cellular Dna ◽  
G Protein Coupled ◽  
Tumor Associated Neutrophils ◽  
Receptor Family

CXCR2, a member of the G-protein-coupled cell surface chemokine receptor family, is commonly found on leukocytes, endothelial cells and tumor cells including nasopharyngeal carcinoma cells. However, how the activity of CXCR2 and its ligand CXCL8 affects the development of nasopharyngeal carcinoma (NPC) remains unknown. Here, we found that CXCR2 and CXCL8 were both predicted poor prognosis in NPC patients. Furthermore, we identified that treatment with CXCR2 antagonist SB225002 of nasopharyngeal carcinoma cell lines resulted tumorigenesis inhibition in vitro and in vivo. In addition, we found that SB225002 could enhance NPC cells radiosensitivity through regulating cell circle distribution and interfering with cellular DNA damage repair. SB225002 also exhibited an efficient radiosensitization effect in C666-1 and HONE-1 bearing mice. Functionally, we showed that SB225002 reduced microvessel density and proliferation and induced tumor apoptosis. Furthermore, changes in the tumor microenvironment were also observed in this study. We observed that SB225002 reduced tumor-associated neutrophils (TANs) in the tumors tissue which were recruited especially after irradiation. Taken together, our results suggested that targeting the CXCL8-CXCR2 pathway is a promising therapeutic strategy for comprehensive NPC treatment.

scholarly journals Apogossypolone induces apoptosis and autophagy in nasopharyngeal carcinoma cells in an in vitro and in vivo study

2017 ◽  
Vol 14 (1) ◽  
pp. 751-757 ◽  
Author(s):  
Ruinian Zheng ◽  
Kexu Chen ◽  
Yu Zhang ◽  
Jie Huang ◽  
Fengrong Shi ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Carcinoma Cells ◽  
In Vivo Study

MiR-30a-5p inhibits proliferation, migration and invasion of nasopharyngeal carcinoma cells by targeting NUCB2

2021 ◽  
pp. 096032712199191
Author(s):  
M Li ◽  
Y Wang ◽  
Q Zhao ◽  
W Ma ◽  
J Liu
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Growth ◽  
Carcinoma Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Binding Interaction ◽  
Downstream Target ◽  
Downstream Target Gene

Background: Nasopharyngeal carcinoma (NPC) is a malignant head and neck tumor arising in the nasopharynx. MicroRNAs (miRNAs) are elucidated to exert tumor-suppressing function in human cancers. Numerous studies have manifested that miR-30a-5p serves as an anti-oncogene in various cancers. Objective: To research the biological function and molecular mechanism of miR-30a-5p in NPC. Methods: The morphology of NPC tissues was revealed by H&E staining. Transwell and wound healing assays were applied to investigate the effects of miR-30a-5p on NPC cell migration. The binding interaction between miR-30a-5p and nucleobindin 2 (NUCB2) was identified by luciferase reporter assay. Xenograft nude mice were used to detect the influence of miR-30a-5p on NPC tumor growth. Results: MiR-30a-5p was downregulated in NPC tissues and cells. The overexpression ofmiR-30a-5p inhibited proliferation, migration and invasion abilities of NPC cells. Moreover, NUCB2 was revealed to be a downstream target gene of miR-30a-5p, and knockdown of NUCB2 repressed the malignant behaviors of NPC cells and tumor growth. Additionally, rescue experiments revealed that miR-30a-5p suppressed the proliferation, migration and invasion of NPC cells via targeting NUCB2 in vitro. Meanwhile, in vivo assays depicted that NUCB2 overexpression rescued the effects induced by miR-30a-5p upregulation on tumor growth. Conclusion: MiR-30a-5p modulates NPC progression by targeting NUCB2. These findings lay a foundation for exploring the clinical treatment of NPC.

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