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学科主题: 口腔医学
题名:
Activating PTEN by COX-2 inhibitors antagonizes radiation-induced MKT activation contributing to radiosensitization
作者: Meng, Zhen1,2; Gan, Ye-Hua1,2
关键词: Radiation ; PTEN ; ART ; COX-2 ; Celecoxib ; Valdecoxib
刊名: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
发表日期: 2015-05-01
DOI: 10.1016/j.bbrc.2015.03.008
卷: 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
所属项目编号: 81472764 ; 2013DFB30360
项目资助者: National Natural Science Foundation of China ; China International Science and Technology Cooperation
WOS记录号: WOS:000354230300012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50396
Appears in Collections:北京大学口腔医学院_期刊论文

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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

Recommended Citation:
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.
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