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Activating PTEN by COX-2 inhibitors antagonizes radiation-induced MKT activation contributing to radiosensitization
Meng, Zhen1,2; Gan, Ye-Hua1,2
关键词Radiation Pten Art Cox-2 Celecoxib Valdecoxib
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
2015-05-01
DOI10.1016/j.bbrc.2015.03.008
460期:2页:198-204
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]NF-KAPPA-B ; TUMOR-SUPPRESSOR PTEN ; CANCER CELLS ; LUNG-CANCER ; PATHWAY ; PROTEIN ; AKT ; PHOSPHORYLATION ; EXPRESSION ; CELECOXIB
英文摘要

Radiotherapy is still one of the most effective nonsurgical treatments for many tumors. However, radioresistance remains a major impediment to radiotherapy. Although COX-2 inhibitors can induce radiosensitization, the underlying mechanism is not fully understood. In this study, we showed that COX-2 selective inhibitor celecoxib enhanced the radiation-induced inhibition of cell proliferation and apoptosis in HeLa and SACC-83 cells. Treatment with celecoxib alone dephosphorylated phosphatase and tensin homolog deleted on chromosome ten (PTEN), promoted PTEN membrane translocation or activation, and correspondingly dephosphorylated or inactivated protein kinase B (ART). By contrast, treatment with radiation alone increased PTEN phosphorylation, inhibited PTEN membrane translocation and correspondingly activated AKT in the two cell lines. However, treatment with celecoxib or another COX-2 selective inhibitor (valdecoxib) completely blocked radiation-induced increase of PTEN phosphorylation, rescued radiation-induced decrease in PTEN membrane translocation, and correspondingly inactivated ART. Moreover, celecoxib could also upregulate PTEN protein expression by downregulating Sp1 expression, thereby leading to the activation of PTEN transcription. Our results suggested that COX-2 inhibitors could enhance radiosensitization at least partially by activating PTEN to antagonize radiation-induced AICT activation. (C) 2015 Elsevier Inc. All rights reserved.

语种英语
WOS记录号WOS:000354230300012
项目编号81472764 ; 2013DFB30360
资助机构National Natural Science Foundation of China ; China International Science and Technology Cooperation
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50396
专题北京大学口腔医学院
北京大学口腔医学院_中心实验室
作者单位1.Peking Univ, Sch & Hosp Stomatol, Cent Lab, Beijing 100081, Peoples R China
2.Peking Univ, Sch & Hosp Stomatol, Dept Oral & Maxillofacial Surg, Beijing 100081, Peoples R China
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GB/T 7714
Meng, Zhen,Gan, Ye-Hua. Activating PTEN by COX-2 inhibitors antagonizes radiation-induced MKT activation contributing to radiosensitization[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2015,460(2):198-204.
APA Meng, Zhen,&Gan, Ye-Hua.(2015).Activating PTEN by COX-2 inhibitors antagonizes radiation-induced MKT activation contributing to radiosensitization.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,460(2),198-204.
MLA Meng, Zhen,et al."Activating PTEN by COX-2 inhibitors antagonizes radiation-induced MKT activation contributing to radiosensitization".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 460.2(2015):198-204.
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