[1]李浩男,彭柯峥,师莹莹,等.OP16联合雷帕霉素对人食管鳞癌裸鼠移植瘤生长和细胞凋亡的影响[J].郑州大学学报(医学版),2018,(01):5-9.[doi:10.13705/j.issn.1671-6825.2017.10.014]
 LI Haonan,PENG Kezheng,SHI Yingying,et al.Effects of OP16 combined with rapamycin on growth and cell apoptosis of human esophageal squamous cell carcinoma xenograft in nude mice[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2018,(01):5-9.[doi:10.13705/j.issn.1671-6825.2017.10.014]
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OP16联合雷帕霉素对人食管鳞癌裸鼠移植瘤生长和细胞凋亡的影响()
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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:
5-9
栏目:
食管癌研究
出版日期:
2018-01-20

文章信息/Info

Title:
Effects of OP16 combined with rapamycin on growth and cell apoptosis of human esophageal squamous cell carcinoma xenograft in nude mice
作者:
李浩男彭柯峥师莹莹刘小林曹燕君郝雨桐覃佳宁侯桂琴
郑州大学药学院临床药学系 郑州 450001
Author(s):
LI Haonan PENG Kezheng SHI Yingying LIU Xiaolin CAO Yanjun HAO Yutong QIN Jianing HOU Guiqin
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001
关键词:
雷帕霉素 OP16 食管鳞癌 mTOR 裸鼠
Keywords:
rapamycin OP16 esophageal squamous cell carcinoma mTOR nude mice
分类号:
R735.1
DOI:
10.13705/j.issn.1671-6825.2017.10.014
摘要:
目的:探讨新型冬凌草甲素衍生物OP16和mTOR抑制剂雷帕霉素对人食管鳞癌裸鼠移植瘤生长和凋亡的影响及可能的分子机制。方法:建立人食管鳞癌EC9706细胞的裸鼠移植瘤模型,随机分为对照组、OP16组、雷帕霉素组和联合治疗组,每组10只。观察经过治疗后荷瘤裸鼠的肿瘤生长情况,使用TUNEL法检测各组肿瘤组织中细胞凋亡情况,并使用Western blot法检测裸鼠肿瘤组织中PI3K/Akt/mTOR通路相关蛋白的表达情况。结果:OP16和雷帕霉素单独给药均能抑制肿瘤的生长,二者联用抑制效果更为明显(FOP16=17.562,F雷帕霉素=18.302,F交互=20.716,P<0.001)。TUNEL结果表明OP16和雷帕霉素单独给药均能促进肿瘤细胞凋亡,且二者联用时促凋亡能力增强(FOP16=209.515,F雷帕霉素=230.235,F交互=445.186; P<0.001)。Western blot结果表明,OP16可以显著抑制雷帕霉素引起的PI3K/Akt负反馈激活(P<0.01),且二者联用可以协同抑制mTOR的表达及磷酸化激活(P<0.05)。结论:OP16与雷帕霉素联用具有较好的协同抑制肿瘤生长以及促进肿瘤细胞凋亡的作用,其分子机制可能与对PI3K/Akt/mTOR信号通路的抑制作用有关。
Abstract:
Aim: To evaluate the effects of a novel derivative of oridonin OP16 and a mTOR inhibitor rapamycin used alone or in combination on the growth and cell apoptosis of human esophageal squamous cell carcinoma xenograft in nude mice and its possible mechanisms.Methods: EC9706 cells were subcutaneously inoculated into nude mice to establish a subcutaneous transplantation tumor model. Mice were randomly allocated into control group, OP16 group, rapamycin group and combined treatment group. After treatment, the growth of xenografted tumor was observed and recorded, and the apoptosis of xenografted tumor cells was explored by TUNEL assay. Moreover, the expressions of PI3K/Akt/mTOR signaling pathway related proteins were investigated by Western blot.Results: OP16 or rapamycin alone could significantly inhibit tumor growth in xenograft mice,and the combination of them produced greater inhibition effect on tumor growth than either agent alone(FOP16=17.562,Frapamycin=18.302,Finteraction=20.716; P<0.001). The results of TUNEL assay demonstrated that OP16 and rapamycin alone could promote apoptosis of xenografted tumor cells, and the combination of them existed greater pro-apoptotic activity than either agent alone(FOP16=209.515,Frapamycin=230.235,Finteraction=445.186; P<0.001). The results of Western blot showed that OP16 could significantly inhibit rapamycin-induced PI3K/Akt activation(P<0.01), and the combination of them could synergistically inhibit the expression and phosphorylation of mTOR(P<0.05).Conclusion: The combination of OP16 and rapamycin has synergistic effects on tumor growth inhibition and cell apoptosis induction in nude mice, and the possible molecular mechanisms underlying the synergistic effect is related to the down-regulation of PI3K/Akt/mTOR signaling pathway.

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备注/Memo

备注/Memo:
【基金项目】河南省基础与前沿技术研究计划项目(162300410122); 郑州大学大学生创新创业训练计划项目(201610459083)
【作者简介】侯桂琴,通信作者,女,1977年6月生,博士,副教授,研究方向:肿瘤药理和肿瘤细胞分子生物学,E-mail: hougq@zzu.edu.cn
更新日期/Last Update: 2018-01-20