|本期目录/Table of Contents|

[1]吴锦欢,陈玉平,李 磊,等.ATR抑制剂VX-970对CPT诱导的结肠癌细胞生长的影响[J].天津医科大学学报,2018,24(05):376-380384.
 WU Jin-huan,CHEN Yu-ping,LI Lei,et al.Effect of ATR inhibitor VX-970 on the growth of colorectal cancer cell induced by CPT[J].Journal of Tianjin Medical University,2018,24(05):376-380384.
点击复制

ATR抑制剂VX-970对CPT诱导的结肠癌细胞生长的影响(PDF)
分享到:

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
24卷
期数:
2018年05期
页码:
376-380384
栏目:
基础医学
出版日期:
2018-09-20

文章信息/Info

Title:
Effect of ATR inhibitor VX-970 on the growth of colorectal cancer cell induced by CPT
作者:
吴锦欢1陈玉平2李 磊2薛 颖2李振鑫1乔海晅1袁 建2
1. 天津医科大学生物医学工程与技术学院,天津300070;2.同济大学附属东方医院,心率失常教育部重点实验室,上海200120
Author(s):
WU Jin-huan1 CHEN Yu-ping2 LI Lei2 XUE Ying2 LI Zhen-xin1 QIAO Hai-xuan1 YUAN Jian2
1. School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin 300070, China;2. Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China
关键词:
VX-970喜树碱凋亡结肠癌细胞生长
Keywords:
VX-970CPTapoptosis colorectal cancer cellsgrowth
分类号:
R735.3+5
DOI:
-
文献标志码:
A
摘要:
目的:探讨ATR特异抑制剂VX-970对喜树碱抑制的结肠癌细胞HCT-116生长,促进结肠癌细胞HCT-116凋亡的影响。方法:采用克隆形成、MTS、流式细胞术等实验分别检测单独使用VX-970,CPT以及联合VX-970和CPT用药处理对细胞生长、细胞周期及凋亡等影响,蛋白免疫印迹检测DNA损伤关键蛋白p-ATR,p-Chk1,γH2AX等的表达。结果:VX-970增强CPT对HCT-116细胞生长和增殖的抑制作用,促进细胞凋亡和减弱细胞周期G2/M期的阻滞。结论:VX-970能显著增强CPT抑制HCT-116细胞生长,诱导细胞凋亡和提高细胞对CPT药物的敏感性。
Abstract:
Objective: To investigate the effect of VX-970, an ATR specific inhibitor, on growth and apoptosis induced by CPT in colorectal cancer cells. Methods: Upon absence or presence of VX970 in CPT treatment for colorectal cancer cells, cell survival, proliferation, cell cycle and apoptosis were detected by colony forming, MTS and cell flow cytometry; the expression of DNA damage response key proteins(p-ATR, p-Chk1, γH2AX) was detected by Western blot. Results: VX-970 enhanced the effect of CPT on inhibiting proliferation, promoted cell apoptosis and induced cell cycle G2/M phase arrest. Conclusion: Combining CPT with VX-970 could significantly inhibit the growth and apoptosis and sensitize human colorectal cancer cells to CPT.

参考文献/References:


[1] 聂磊,薛迎利,李雅,等. 托泊替康与伊立替康单药治疗老年小细胞肺癌的疗效观察[J].现代肿瘤医学,2017,25(6):905
[2] 孙佳,李胜范,郑丽丽. ATM /ATR 在DNA 损伤反应中的作用[J].中华临床医师杂志,2011,5(6):1683
[3] Zhang P,Wei Y,Wang L,et al. ATM-mediated stabilization of ZEB1 promotes DNA damage response and radioresistance through CHK1[J].Nat Cell Biol,2014,16(9):864
[4] 王晓娜,任来峰,赵安江,等. 3-甲基腺嘌呤对喜树碱诱导的宫颈癌Hela细胞凋亡的影响[J].中国免疫学杂志,2016,32(8):1128
[5] Jossé R,Martin S E,Guha R,et al. ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses[J].Cancer Res,2014,74(23):6968
[6] Hall A B,Newsome D,Wang Y,et al. Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970[J]. Oncotarget,2014,5(14):5674
[7] Fokas E,Prevo R,Pollard J R,et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation[J]. Cell Death Dis,2012,3:e441
[8] Lord C J,Ashworth A. The DNA damage response and cancer therapy[J]. Nature,2012,481(7381):287
[9] Massey A J. Inhibition of ATR-dependent feedback activation of Chk1 sensitises cancer cells to Chk1 inhibitor monotherapy[J].Cancer Lett,2016,383(1):41
[10] Huntoon C J,Flatten K S,Wahner Hendrickson A E,et al. ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy Independent of BRCA status[J]. Cancer Res,2013,73(12):3683
[11] Li W,Saud S M,Young M R,et al. Cryptotanshinone,a Stat3 inhibitor,suppresses colorectal cancer proliferation and growth in vitro[J]. Mol Cell Biochem,2015,406(1/2):63
[12] Jackson S P,Bartek J. The DNA-damage response in human biology and disease[J]. Nature,2009,461(7267):1071
[13] Reaper P M,Griffiths M R,Long J M,et al. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR[J].Nat ChemBiol,2011,7(7):428
[14] Massey A J. Inhibition of ATR-dependent feedback activation of Chk1 sensitises cancer cells to Chk1 inhibitor monotherapy[J].Cancer Lett,2016,383(1):41
[15] Shigechi T,Tomida J,Sato K,et al. ATR-ATRIP kinase complex triggers activation of the Fanconi anemia DNA repair pathway[J].Cancer Res,2012,72(5):1149
[16] Singh T R,Ali A M,Paramasivam M,et al. ATR-dependent phosphorylation of FANCM at serine 1045 is essential for FANCM functions[J]. Cancer Res,2013,73(14):4300

相似文献/References:

备注/Memo

备注/Memo:
-
更新日期/Last Update: 2018-09-30