[1]张 乐),李庆华),杨 璐),等.DZNep对裸鼠食管鳞癌移植瘤生长的抑制作用[J].郑州大学学报(医学版),2018,(01):17-21.[doi:10.13705/j.issn.1671-6825.2017.02.060]
 ZHANG Le),LI Qinghua),YANG Lu),et al.Inhibition effects of DZNep on growth of esophageal squamous cell carcinoma xenograft in nude mice[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2018,(01):17-21.[doi:10.13705/j.issn.1671-6825.2017.02.060]
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DZNep对裸鼠食管鳞癌移植瘤生长的抑制作用()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2018年01期
页码:
17-21
栏目:
食管癌研究
出版日期:
2018-01-20

文章信息/Info

Title:
Inhibition effects of DZNep on growth of esophageal squamous cell carcinoma xenograft in nude mice
作者:
张 乐1)李庆华1)杨 璐1)朱立强2)张彦婷1)关方霞1)
1)郑州大学生命科学学院 郑州 450001 2)郑州大学第二附属医院检验科 郑州 450014
Author(s):
ZHANG Le1)LI Qinghua1)YANG Lu1)ZHU Liqiang2)ZHANG Yanting1)GUAN Fangxia1)
1)School of Life Sciences, Zhengzhou University, Zhengzhou 450001 2)Clinical Laboratory, the Second Affiliated Hospital, Zhengzhou University, Zhengzhou 450014
关键词:
食管鳞癌 EZH2抑制剂 DZNep 裸鼠 mTOR/p70S6K信号通路
Keywords:
esophageal squamous cell carcinoma inhibitor of EZH2 DZNep nude mouse mTOR/p70S6K signaling pathway
分类号:
R735.1
DOI:
10.13705/j.issn.1671-6825.2017.02.060
摘要:
目的:探讨EZH2抑制剂DZNep对裸鼠Eca109细胞移植瘤生长及mTOR/p70S6K信号通路的影响。方法:将Eca109细胞接种于15只裸鼠右侧背部皮下构建裸鼠移植瘤模型后分为3组,每组5只,其中2组分别腹腔注射5-氟尿嘧啶(5-FU)、DZNep治疗2周,另外1组腹腔注射生理盐水作为对照组。观察肿瘤生长情况,采用Western blot检测肿瘤组织中EZH2、SAHH、组蛋白甲基化相关蛋白及mTOR/p70S6K信号通路相关蛋白、Caspase-3、E-cadherin的表达情况,并通过TUNEL法检测肿瘤组织中细胞的凋亡,计算细胞凋亡率。结果:DZNep组肿瘤块质量小于对照组(P<0.05)。与对照组比较,DZNep组肿瘤组织中Caspase-3和E-cadherin表达水平增高,细胞凋亡率升高(P<0.05)。另外,与对照组相比,DZNep组H3K27me3表达降低,PTEN表达升高,mTOR和p-p70S6K表达均下降(P<0.05)。结论:DZNep可抑制食管鳞癌移植瘤增长,并诱导肿瘤细胞凋亡; 其机制可能是通过对EZH2的抑制增强PTEN的表达,从而抑制mTOR/p70S6K信号通路的激活。
Abstract:
Aim: To observe the effects of DZNep on the growth of esophageal squamous cell carcinoma(ESCC)xenograft and mTOR/p70S6K signaling pathway in vivo.Methods: Eca109 cells were injected into 15 nude mice to establish Eca109 cell xenograft mouse model. These 15 mice were randomly allocated into 3 groups. Mice in one group were intra-peritoneally injected with 5-FU every other day for 2 weeks, mice in one group were injected with DZNep, and mice in the last group were injected with normal saline as control. Then, Western blot was employed to detect the expressions of EZH2, SAHH, histone methylation related protein, mTOR/p70S6K signal pathway related protein, Caspase-3, and E-cadherin in tumor tissue. And TUNEL was used to detect the cell apoptosis in tumor.Results: The tumor weight was decreased significantly in DZNep group compared with that in control group(P<0.05). Meanwhile, the expression of Caspase-3 and E-cadherin and the apoptosis rate were increased significantly in tumor tissue of DZNep group(P<0.05). The expression of PTEN was increased, and the expressions of H3K27me3, mTOR and phosphorylated p70S6K were decreased in DZNep group(P<0.05).Conclusion: DZNep could inhibit ESCC xenograft growth and promote ESCC cell apoptosis in vivo, by inhibiting the activation of mTOR/p70S6K signal pathway.

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备注/Memo

备注/Memo:
【基金项目】河南省高等学校重点科研项目(15A310028,15A180022)
【作者简介】关方霞,通信作者,女,1969年2月生,博士,教授,研究方向:生物医学,E-mail:fxguan@126.com; 李庆华,通信作者,女,1983年6月生,博士,讲师,研究方向:肿瘤学,E-mail:guozilqh@126.com
更新日期/Last Update: 2018-01-20