EZH2过表达在MCF-7获得性耐药中的作用

doi:10.11904/j.issn.1002-3070.2016.02.006

Abstract

Abstract: Objective To explore the effect of EZH2 overexpression on acquired drug resistance in MCF-7 cells.Methods The relative expressions of EZH2 mRNA and protein of MCF-7 and MCF-7/ADR were detected respectively by real time fluorescence quantitative PCR(RTFQPCR)and Western-blot.After EZH2 shRNA and EZH2 shRNA-scramble plasmid vectors with reporter gene EGFP were transfected into MCF-7/ADR cells,the stable cell line was screened by G4l8.RTFQPCR was used to validate whether the EZH2 mRNA in EZH2 shRNA group was supressed.The differences of the effect of adriamycin on cell proliferation were evaluated among EZH2 shRNA goup,EZH2 shRNA-scramble group and negative control groups using WST-1 assays.Results The EZH2 mRNA and protein expression levels in MCF-7/ADR cells were 2.52±1.523 and 1.58±0.58 folds of those in MCF-7cells.The differences were significant(P＜0.05).After the EZH2 shRNA plasmid was stably expressed in MCF-7/ADR cells,the expressions of EZH2 mRNA were decreased by 84%(P＜0.05)and the cell proliferation was decreased by 25% after adriamycin(P＜0.05),However there were no significant changes of cell proliferation in EZH2 shRNA-scramble group and negative control groups after adriamycin.Conclusion EZH2 was overexpressed in MCF-7/ADR cells compared with MCF-7 cells.Silencing EZH2 may effectively reverse the resistance of MCF-7/ADR cells to adriamycin.

Key words: EZH2, MCF-7/ADR, Adriamycin resistance

CLC Number:

R737.9

ZHAO Ling, HE Jinqi, BAI Shuping, GUO Li, WANG Xiaohong. The effect of EZH2 overexpression on acquired drug resistance in MCF-7 cells[J]. PRACTICAL ONCOLOGY JOURNAL, 2016, 30(2): 123-127.

References

1 Ding X,Wang X,Sontag S,et al.The polycomb protein Ezh2 impacts on induced pluripotent stem cell generation[J].Stem Cells Dev,2014,23(9):931-940.
2 Pang J,Toy KA,Griffith KA,et al.Invasive breast carcinomas in Ghana:high frequency of high grade,basal-like histology and high EZH2 expression[J].Breast Cancer Res Treat,2012,135(1):59-66.
3 Panousis D,Patsouris E,Lagoudianakis E,et al.The value of TOP2A,EZH2 and paxillin expression as markers of aggressive breast cancer:relationship with other prognostic factors[J].Eur J Gynaecol Oncol,2011,32(2):156-159.
4 Sellers WR,Loda M.The EZH2 polycomb transcriptional repressor-a marker or mover of metastatic prostate cancer[J].Cancer Cell,2002,2(5):349-350.
5 van Kemenade FJ,Raaphorst FM,Blokzijl T,et al.Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma[J].Blood,2001,97(12):3896-3901.
6 Liudmila LK,Rutger JJ,Jarom H,et al.The role of EZH2 and DNA methylation in the silencing of the tumour suppressor RUNX3 in colorectal cancer[J].Carcinogenesis,2010,9(32):1567-1575.
7 Liu L,Xu Z,Zhong L,et al.Enhancer of zeste homolog 2(EZH2)promotes tumour cell migration and invasion via epigenetic repression of E-cadherin in renal cell carcinoma[J].BJU Int,2016,117(2):351-362.
8 胡沙,王静,李智敏,等.EZH2基因在人卵巢癌顺铂耐药株中的表达及其对细胞耐药性的影响[J].肿瘤,2010,9(30):748-751.
9 田金华,王晶,宋成文,等.EZH2与人卵巢上皮性癌细胞顺铂耐药性的相关性[J].华南国防医学杂志,2011,25(3):193-195.
10 Cai L,Wang Z,Liu D.Interference with endogenous EZH2 reverses the chemotherapy drug resistance in cervical cancer cells partly by up-regulating Dicer expression[J].Tumour Biol,2015,2[Epub ahead of print].
11 Ginsburg OM,Love RR.Breast cancer:a neglected disease for the majority of affected women worldwide[J].Breast J,2011,17(3):289-295.
12 Lund K,Adams PD,Copland M.EZH2 in normal and malignant hematopoiesis[J].Leukemia,2014,28(1):44-49.
13 Tan JZ,Yan Y,Wang XX,et al.EZH2:biology,disease,and structure-based drug discovery[J].Acta Pharmacol Sin,2014,35(2):161-174.
14 Margueron R,Reinberg D.The Polycomb complex PRC2 and its mark in life[J].Nature,2011,469(7330):343-349.
15 Fu YB,Chen J,Pang B,et al.EZH2-induced H3K27me3 is associated with epigenetic repression of the ARHI tumor-suppressor gene in ovarian cancer[J].Cell Biochemistry and Biophysics,2015,71(1):105-112.
16 Gonzalez ME,Duprie ML,Krueger H,et al.Histone methyltransferase EZH2 induces Akt-dependent genomic instability and BRCA1 inhibition in breast cancer[J].Cancer Res,2011,71(6):2360-2370.
17 Raaphorst FM,Meijer CJ,Fieret E,et al.Poorly differentiated breast carcinoma is associated with increased expression of the human polycomb group EZH2 gene[J].Neoplasia,2003,5(6):481-488.
18 Yaser RH,Anil KS,Sudeshna B,et al.Clinical and biological relevance of EZH2 in triple negative breast cancer[J].Hum Pathol,2012,43(10):1638-1644.
19 Zhou W,Wang J,Man WY,et al.SiRNA silencing EZH2 reverses cisplatin-resistance of human non-small cell lung and gastric cancer cells[J].Asian Pac J Cancer Prev,2015,16(6):2425-2430.
20 Wang HL,Yu YH,Chen C,et al.Involvement of enhancer of zeste homolog 2 in cisplatin-resistance in ovarian cancer cells by interacting with several genes[J].Mol Med Rep,2015,12(2):2503-2510.

[1]	WANG Xiaoya,XIAO Bin,LIAO Yang,TANG Rongzhi,SUN Zhaohui,LI Linhai. Expression of CXCR family proteins in different subtypes of breast cancer and their clinical prognosis [J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(3): 206-210.
[2]	CHEN Yanbo, KONG Dejia, ZHANG Jinfeng, MA Zhigang. Correlation between CYP2D6 gene polymorphism and tamoxifen metabolism in breast cancer patients [J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(2): 110-114.
[3]	SUN Jianghong, HAO Mingzhu, JIANG Dan, GUO Fei, LI Xiaomei. FFDM differential diagnosis of mastitis,benign hyperplasia and breast cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(2): 139-141.
[4]	MA Zhijie, WANG Fan, ZHAO Yashuang. Analysis of life quality and influencing factors in breast cancer patients with chemotherapy [J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(2): 149-154.
[5]	BAI Yuxian, MA Zhongjuan, SU Yingling, MU Anguo, XIE Rui. Research on methylation of FHIT,hMLH1,p16,RAR-beta,Reprimo and TIMP3 genes in gastric cancer patients [J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(1): 8-13.
[6]	MA Zhingying, SHANG Naijian, CAI Miaotian, SHEN Yang, JIANG Zhiyun. Correlation between HER-2 receptor of progesterone and estrogen receptor-positive breast cancer and mammography imaging & clinicopathological features [J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(1): 47-51.
[7]	HE Xu, YE shangmian, DONG dandan, LI Ke. The expression of HLA-G in breast cancer and its significance [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(5): 410-414.
[8]	WANG Zhi,LIU Zhongwei,ZENG Xueyun,SUI Mingjie,LIAO Jingyi,LI Yuehuan,HUANG Weidong,LIU Guoxiang. Health-related quality of life in patients with colorectal cancer precancerous lesions on EQ-5D-5L [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(4): 320-326.
[9]	FAN Ningning, GENG Jingshu. The expression and role of LncRNA MEG3 in human glioma cells [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(3): 219-223.
[10]	YAN Shi, HUO Mingming, PANG Hui, LI Yan, CAI Li. Effects of p53 on predictive value for efficacy of endocrine drugs in postoperative postmenopausal breast cancer patients with HR positive and HER-2 positive [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(3): 234-213.
[11]	LI Lin, LI Zhigao. The relationship between metformin and different molecular subtypes of breast cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(3): 267-270.
[12]	JIN Junjie, AN Jing, CAO Difei, SONG Aili, ZHAO Lili, LIU Zhaoliang. Construction and identification of shRNA lentiviral vectors targeting histone lysine transferase KAT6B gene [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(1): 1-6.
[13]	ZHENG Wei, XU Shouping, PANG Da. Expression,prognosis and function of long chain non-coding RNA-Linc00152 in breast cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(1): 7-13.
[14]	YIN Yulian, ZHANG Weihong, ZHOU Yue, YE Meina, CHEN Hongfeng. Correlation between single nucleotide polymorphisms of ERα gene and bone loss associated with aromatase inhibitors in postmenopausal women with breast cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(1): 14-18.
[15]	LI Yujiao, SHANG Naijian. Research progress of imaging evaluation of neoadjuvant chemotherapy in breast cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(1): 63-67.

The effect of EZH2 overexpression on acquired drug resistance in MCF-7 cells

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments