|本期目录/Table of Contents|

[1]孟旭英,李珍瑾,郭剑超.组蛋白甲基转移酶EZH2抑制剂联合抗癌药物对膀胱癌细胞功能影响的研究[J].天津医科大学学报,2018,24(01):25-28.
 MENG Xu-ying,LI Zhen-jin,GUO Jian-chao.Effect of histone methyltransferase EZH2 inhibitor combined with anticancer drugs on migration and proliferation of bladder cancer cells[J].Journal of Tianjin Medical University,2018,24(01):25-28.
点击复制

组蛋白甲基转移酶EZH2抑制剂联合抗癌药物对膀胱癌细胞功能影响的研究(PDF)
分享到:

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

卷:
24
期数:
2018年01期
页码:
25-28
栏目:
基础医学
出版日期:
2018-01-20

文章信息/Info

Title:
Effect of histone methyltransferase EZH2 inhibitor combined with anticancer drugs on migration and proliferation of bladder cancer cells
文章编号:
1006-8147(2018)01-0025-04
作者:
孟旭英李珍瑾 郭剑超
(天津医科大学第二医院内分泌科 , 天津 300211)
Author(s):
MENG Xu-ying LI Zhen-jin GUO Jian-chao
( Department of Endocrinology ,The Second Hospital , Tianjin Medical University, Tianjin 300211, China)
关键词:
组蛋白甲基化 UNC1999 丝裂霉素C 表观遗传膀胱癌
Keywords:
histone methylation UNC1999 mitomycin C epigeneticsbladder cancer
分类号:
R737.14
DOI:
-
文献标志码:
A
摘要:
目的:探究组蛋白甲基化酶EZH2特异性抑制剂UNC1999与针对DNA 的化疗药物丝裂霉素C对膀胱癌T24 细胞的抑制效应。方法:组蛋白甲基化酶EZH2特异性抑制剂UNC1999 和化疗药物丝裂霉素C单独使用或者联和使用处理T24细胞,Q-PCR法检测EZH2基因的表达水平,用Western blot法检测EZH2以及下游H3K27me3蛋白的表达水平,MTT法测定T24 细胞的增殖,划痕实验检测细胞的迁移,流式细胞仪检测细胞凋亡。结果:UNC1999与丝裂霉素C单独使用以及联合用药都能引起EZH2表达水平的下调,同时引起T24 细胞增殖能力降低, 迁移能力下降,凋亡水平上调,两者联合使用效果更加明显。结论:UNC1999以及MMC均可引起膀胱癌细胞EZH2表达水平的下调,同时联合使用效果最大, 可明显降低细胞的增殖侵袭能力,上调凋亡水平,为膀胱癌的化疗治疗、用药方法以及后续的机制研究提供了参考。
Abstract:
Objective: To investigate the inhibitory effect of combination of histone methylation enzyme EZH2 specific inhibitor UNC1999 and mitomycin C against bladder cancer T24 cells. Methods: The expression level of EZH2 gene was detected by Q-PCR. The expression of EZH2 gene was detected by Western blot. The expressions of EZH2 and H3K27me3 were detected by Western blot. The cell proliferation was detected by MTT assay. The cell migration of T24 cells was detected by scratch test. Cell apoptosis was detected by flow cytometry. Results: The level of EZH2 expression was down-regulated by UNC1999 and mitomycin C alone and the combined using of mitomycin C could decrease the expression of EZH2, the migration ability of T24 cells was decreased, the migration ability was decreased and the apoptosis level was up-regulated. Conclusion: Both UNC1999 and MMC can down-regulate the expression of EZH2 in bladder cancer cells, and the combining effect is the marked, which can significantly reduce the proliferation and invasion of cells, up-regulate the level of apoptosis, which provides a reference for the treatment of bladder cancer, the method of administration and the follow-up mechanism Research.

参考文献/References:

[1]Bostr?m M M, Irjala H, Mirtti T, et al. Tumor-Associated macrophages provide significant prognostic information in urothelial bladder cancer[J]. PLoS One, 2015, 10(7): e0133552

[2]Hemdan T, Malmstr?m P U, Jahnson S, et al. Emmprin expression predicts response and survival following cisplatin containing chemotherapy for bladder cancer: a validation study[J]. J Urol, 2015, 194(6): 1575

[3]Margueron R, Reinberg D. The polycomb complex PRC2 and its mark in Life[J]. Nature, 2011, 469(7330): 343

[4]Di Croce L, Helin K. Transcriptional regulation by Polycomb group proteins[J]. Nat Struct Mol Biol, 2013, 20(10): 1147

[5]Perdigoto C N, Valdes V J, Bardot E S, et al. Epigenetic regulation of skin: focus on the Polycomb complex[J]. Cell Mol Life Sci, 2012, 69(13): 2161

[6]Müller J, Hart C M, Francis N J, et al. Histone methyltransferase activity of a Drosophila Polycomb group repressor complex[J]. Cell, 2002, 111(2): 197

[7]Deb G, Singh A K, Gupta S. EZH2: not EZHY (easy) to deal[J]. Mol Cancer Res, 2014, 12(5): 639.

[8]Knutson S K, Wigle T J, Warholic N M, et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells[J]. Nat Chem Biol, 2012, 8(11): 890

[9]Knutson S K, Kawano S, Minoshima Y, et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma[J]. Mol Cancer Ther, 2014, 13(4): 842

[10]Chen W, Zheng R, Baade P D, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115

[11]Dalgliesh G L, Furge K, Greenman C, et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes[J]. Nature, 2010, 463(7279): 360

[12]Gui Y T, Guo G W, Huang Y, et al. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder[J]. Nat Genet, 2011, 43(9): U84

[13]Ho A S, Kannan K, Roy D M, et al. The mutational landscape of adenoid cystic carcinoma[J]. Nat Genet, 2013, 45(7): 791

[14]Varambally S, Dhanasekaran S M, Zhou M, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer[J]. Nature, 2002, 419(697): 624

[15]Raman J D, Mongan N P, Tickoo S K, et al. Increased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder[J]. Clin Cancer Res, 2005, 11(24 Pt 1): 8570

[16]Hinz S, Weikert S, Magheli A, et al. Expression profile of the polycomb group protein enhancer of Zeste homologue 2 and its prognostic relevance in renal cell carcinoma[J]. J Urol, 2009, 182(6): 2920

[17]Kim K H, Kim L, Choi S J, et al. The clinicopathological significance of epithelial mesenchymal transition associated protein expression in head and neck squamous cell carcinoma[J]. Korean J Pathol, 2014, 48(4): 263

[18]Ahani N, Shirkoohi R, Rokouei M, et al. Overexpression of enhancer of zeste human homolog 2 (EZH2) gene in human cytomegalovirus positive glioblastoma multiforme tissues[J]. Med Oncol, 2014, 31(11): 252

[19]Yu J, Yu J, Rhodes D R, et al. A polycomb repression signature in metastatic prostate cancer predicts cancer outcome[J]. Cancer Res, 2007, 67(22): 10657

[20]Gonzalez M E, Moore H M, Li X, et al. EZH2 expands breast stem cells through activation of NOTCH1 signaling[J]. Proc Natl Acad Sci U S A, 2014, 111(8): 3098

[21]Van Vlerken L E, Kiefer C M, Morehouse C, et al. EZH2 is required for breast and pancreatic cancer stem cell maintenance and can be used as a functional cancer stem cell reporter[J]. Stem Cells Transl Med, 2013, 2(1): 43

[22]De Santis M, Bachner M. New developments in first- and second-line chemotherapy for transitional cell, squamous cell and adenocarcinoma of the bladder[J]. Curr Opin Urol, 2007, 17(5): 363

[23]Stirzaker C, Song J Z, Davidson B, et al. Transcriptional gene silencing promotes DNA hypermethylation through a sequential change in chromatin modifications in cancer cells[J]. Cancer Res, 2004, 64(11): 3871

相似文献/References:

备注/Memo

备注/Memo:
作者简介 孟旭英(1983-),女, 医师,研究方向:内分泌学; E-mail: xuxuhehuihui@163.com
更新日期/Last Update: 2018-01-19