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Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells
Zhang, Jinhua1,2,3; Si, Jing1,2,3; Gan, Lu1,2,3; Guo, Menghuan4; Yan, Junfang1,2,3; Chen, Yuhong1,2,3; Wang, Fang1,2,3; Xie, Yi1,2,3; Wang, Yupei1,2,3; Zhang, Hong1,2,3
刊名ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
2020
卷号48期号:1页码:479-487
关键词C-12(6+) irradiation cervical carcinoma Wnt beta-catenin pathway XAV939 radio-sensitivity
ISSN号2169-1401
DOI10.1080/21691401.2020.1716779
通讯作者Si, Jing(sijing@impcas.ac.cn) ; Zhang, Hong(zhangh@impcas.ac.cn)
英文摘要Cervical cancer is the second most common malignant tumour threatening women's health. In recent years, heavy-ion beam therapy is becoming a newly emerging therapeutic mean of cancer; however, radio-resistance and radiation-induced damage constitute the main obstacles for curative treatment of cervical cancer. Therefore, to identify the radiosensitizers is essential. Here, we investigated the effects of Wnt signalling pathway on the response of C-12(6+) radiation in HeLa cells. XAV939, an inhibitor of Wnt signalling pathway, was added two hours before C-12(6+) radiation.C-12(6+) radiation inhibited the viability of HeLa cells in a time-dependent manner, and inhibiting Wnt signalling using XAV939 significantly intensified this stress. Meanwhile, C-12(6+) radiation induced a significant increased cell apoptosis, G2/M phase arrest, and the number of gamma-H2AX foci. Supplementation with XAV939 significantly increased the effects induced by C-12(6+) radiation alone. Combining XAV939 with C-12(6+) irradiation, the expression of apoptotic genes (p53, Bax, Bcl-2) was significantly increased, while the expression of Wnt-related genes (Wnt3a, Wnt5a, beta-catenin, cyclin D1 and c-Myc) was significantly decreased. Overall, these findings suggested that blockage of the Wnt/beta-catenin pathway effectively sensitizes HeLa cells to C-12(6+) irradiation, and it may be a potential therapeutic approach in terms of increasing the clinical efficacy of C-12(6+) beams.
资助项目Ministry of Science and Technology National Key RD Project[2018YFE0205100] ; Key Program of the National Natural Science Foundation of China[U1632270] ; National Natural Science Foundation of China[11675234] ; National Natural Science Foundation of China[11605255] ; National Natural Science Foundation of China[11875061] ; Science and Technology Plan Project of Chengguan district, Lanzhou[2019RCCX0071] ; Lanzhou Talent Innovation and Entrepreneurship Project[2019-RC76]
WOS关键词CARBON-ION RADIOTHERAPY ; WNT/BETA-CATENIN PATHWAY ; DIFFERENTIATION ; IRRADIATION ; ACTIVATION ; CARCINOMA ; RADIATION ; AUTOPHAGY ; IMPACT
WOS研究方向Biotechnology & Applied Microbiology ; Engineering ; Materials Science
语种英语
出版者TAYLOR & FRANCIS LTD
WOS记录号WOS:000509033500001
资助机构Ministry of Science and Technology National Key RD Project ; Key Program of the National Natural Science Foundation of China ; National Natural Science Foundation of China ; Science and Technology Plan Project of Chengguan district, Lanzhou ; Lanzhou Talent Innovation and Entrepreneurship Project
内容类型期刊论文
源URL[http://119.78.100.186/handle/113462/141455]  
专题中国科学院近代物理研究所
通讯作者Si, Jing; Zhang, Hong
作者单位1.Chinese Acad Sci, Inst Modern Phys, Dept Radiat Med, Lanzhou, Peoples R China
2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Peoples R China
3.Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China
4.Lanzhou Univ, Sch Pharm, Lanzhou, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Jinhua,Si, Jing,Gan, Lu,et al. Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells[J]. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY,2020,48(1):479-487.
APA Zhang, Jinhua.,Si, Jing.,Gan, Lu.,Guo, Menghuan.,Yan, Junfang.,...&Zhang, Hong.(2020).Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells.ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY,48(1),479-487.
MLA Zhang, Jinhua,et al."Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells".ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 48.1(2020):479-487.
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