Silencing NFBD1/MDC1 enhances the radiosensitivity of human nasopharyngeal cancer CNE1 cells and results in tumor growth inhibition
作者： Z Wang , Q Zeng , T Chen , K Liao , Y Bu
关键词:
摘要: NFBD1 functions in cell cycle checkpoint activation and DNA repair following ionizing radiation (IR). In this study, we defined the as a tractable molecular target to radiosensitize nasopharyngeal carcinoma (NPC) cells. Silencing using lentivirus-mediated shRNA-sensitized NPC cells dose-dependent manner, increasing apoptotic death, decreasing clonogenic survival delaying damage repair. Furthermore, downregulation of inhibited amplification IR-induced signal, failed accumulate retain damage-response proteins at sites, which leaded defective damage. We also implicated involvement Rad51 DNA-dependent protein kinase catalytic subunit foci formation. Xenografts models nude mice showed that silencing significantly enhanced antitumor activity IR, leading tumor growth inhibition combination therapy. Our studies suggested gene therapy may be an effective strategy for human treatment.
nature.com
sci-hub.se 参考文章(49)
Jogitha Selvarajah, Androulla Elia, Veronica A. Carroll, Abdeladim Moumen, DNA damage-induced S and G2/M cell cycle arrest requires mTORC2-dependent regulation of Chk1 Oncotarget. ,vol. 6, pp. 427- 440 ,(2015) , 10.18632/ONCOTARGET.2813
Edward A Kesicki, Stephen T Schlachter, Adam Kashishian, James Halbrook, Justin G Schiro, Hongmei Huang, Darcey Clark, Heather Douangpanya, C Todd Eary, Larry E Burgess, DNA-dependent protein kinase inhibitors as drug candidates for the treatment of cancer Molecular Cancer Therapeutics. ,vol. 2, pp. 1257- 1264 ,(2003)
Michael B. Kastan, Jiri Bartek, Cell-cycle checkpoints and cancer Nature. ,vol. 432, pp. 316- 323 ,(2004) , 10.1038/NATURE03097
L Chang, P H Graham, J Hao, J Ni, J Bucci, P J Cozzi, J H Kearsley, Y Li, PI3K/Akt/mTOR pathway inhibitors enhance radiosensitivity in radioresistant prostate cancer cells through inducing apoptosis, reducing autophagy, suppressing NHEJ and HR repair pathways Cell Death and Disease. ,vol. 5, ,(2014) , 10.1038/CDDIS.2014.415
Zhenkun Lou, Katherine Minter-Dykhouse, Xianglin Wu, Junjie Chen, MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways Nature. ,vol. 421, pp. 957- 961 ,(2003) , 10.1038/NATURE01447
Niels Mailand, Simon Bekker-Jensen, Helene Faustrup, Fredrik Melander, Jiri Bartek, Claudia Lukas, Jiri Lukas, RNF8 Ubiquitylates Histones at DNA Double-Strand Breaks and Promotes Assembly of Repair Proteins Cell. ,vol. 131, pp. 887- 900 ,(2007) , 10.1016/J.CELL.2007.09.040
Zhenkun Lou, Katherine Minter-Dykhouse, Sonia Franco, Monica Gostissa, Melissa A. Rivera, Arkady Celeste, John P. Manis, Jan van Deursen, André Nussenzweig, Tanya T. Paull, Frederick W. Alt, Junjie Chen, MDC1 Maintains Genomic Stability by Participating in the Amplification of ATM-Dependent DNA Damage Signals Molecular Cell. ,vol. 21, pp. 187- 200 ,(2006) , 10.1016/J.MOLCEL.2005.11.025
Grant S. Stewart, Bin Wang, Colin R. Bignell, A. Malcolm R. Taylor, Stephen J. Elledge, MDC1 is a mediator of the mammalian DNA damage checkpoint Nature. ,vol. 421, pp. 961- 966 ,(2003) , 10.1038/NATURE01446
Markus Löbrich, Penny A. Jeggo, Harmonising the response to DSBs: a new string in the ATM bow DNA Repair. ,vol. 4, pp. 749- 759 ,(2005) , 10.1016/J.DNAREP.2004.12.008
Emmy P. Rogakou, Duane R. Pilch, Ann H. Orr, Vessela S. Ivanova, William M. Bonner, DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139 Journal of Biological Chemistry. ,vol. 273, pp. 5858- 5868 ,(1998) , 10.1074/JBC.273.10.5858