[1]陈玉,亚国伟,张威,等.雷帕霉素靶蛋白RNA干扰联合雷帕霉素对人食管癌移植瘤生长和移植瘤组织中雷帕霉素蛋白基因表达的影响*[J].郑州大学学报(医学版),2009,(06):1135-1137.
 CHEN Yu,YA Guowei,ZHANG Wei,et al.Effects of RNAi combined with rapamycin on expression of mTOR gene in tumor tissue of nude mice transplanted with human esophageal cancer cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2009,(06):1135-1137.
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雷帕霉素靶蛋白RNA干扰联合雷帕霉素对人食管癌移植瘤生长和移植瘤组织中雷帕霉素蛋白基因表达的影响*()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2009年06期
页码:
1135-1137
栏目:
食管癌研究
出版日期:
2009-11-01

文章信息/Info

Title:
Effects of RNAi combined with rapamycin on expression of mTOR gene in tumor tissue of nude mice transplanted with human esophageal cancer cells
作者:
陈玉亚国伟张威陈奎生#
郑州大学第一附属医院病理科;河南省肿瘤病理重点实验室 郑州 450052
Author(s):
CHEN YuYA GuoweiZHANG WeiCHEN Kuisheng
Department of Pathology,the First Affiliated Hospital,Zhengzhou University; Henan Key Laboratory of Tumor Pathology,Zhengzhou 450052
关键词:
雷帕霉素食管肿瘤EC1细胞裸鼠RNA干扰
Keywords:
rapamycin esophageal cancer EC1 cell nude mice RNA interference
分类号:
R735.1
摘要:
探讨RNA干扰技术联合雷帕霉素对人食管癌裸鼠移植瘤生长和移植瘤组织中雷帕霉素靶蛋白(mTOR)基因表达的影响。方法:①构建裸鼠食管癌EC1细胞移植瘤模型,待肿瘤长出1周后,将荷瘤小鼠随机分为雷帕霉素治疗组[(腹腔注射雷帕霉素,50 μg/(kg·次)]、mTOR小分子干扰RNA(siRNA)治疗组[腹腔注射mTOR siRNA,3 μg/次 ]和联合治疗组(先腹腔注射mTOR siRNA,第2天腹腔注射雷帕霉素),另设空白对照组(腹腔注射PBS代替药物)和顺铂治疗组[腹腔注射常规化疗药顺铂,1 mg/(kg·次)];每组各5只。连续治疗2周,治疗结束取瘤组织,分析治疗前后移植瘤体积的变化。②采用免疫组化及原位杂交技术观察各组瘤组织中mTOR蛋白及mRNA的表达。结果:①单用雷帕霉素(F=185.00,P<0.001)或mTOR siRNA(F=199.01,P<0.001)均能降低裸鼠移植瘤体积;雷帕霉素和mTOR siRNA有交互作用(F=30.30,P<0.001),2者联合应用后,裸鼠移植瘤体积有更大幅度的下降。顺铂治疗后,裸鼠移植瘤体积与联合治疗的效果差异无统计学意义(t=0.426,P=0.682)。②单用雷帕霉素(F=395.76,F=550.04,P均<0.001)或mTOR siRNA(F=367.58,F=573.39,P均<0.001)均能降低裸鼠移植瘤组织中mTOR蛋白及 mRNA的表达;雷帕霉素和mTOR siRNA有交互作用(F=11.68,P=0.004;F=10.23,P=0.006),2者联合应用后,裸鼠移植瘤组织中mTOR蛋白及 mRNA的表达有更大幅度的下降。顺铂治疗后,裸鼠移植瘤组织中mTOR蛋白(7.15±0.56)及 mRNA(6.88±0.59)的表达与联合治疗的效果差异无统计学意义(t=0.622,P=0.551;t=0.572,P=0.583)。结论:应用RNA干扰技术沉默mTOR基因及应用雷帕霉素治疗均可有效抑制肿瘤的生长,下调裸鼠食管癌移植瘤组织中mTOR蛋白及mRNA的表达,且2者联合效果最佳。
Abstract:
To investigate the effects of the RNA interference(RNAi) and rapamycin on the expression of the target protein of rapamycin(mTOR) in human esophageal carcinoma xenografts of the nude mice.Methods:The models of human esophageal carcinoma xenografts in nude mice were established, after a week of the tumor growth,they were randomly divided into the rapamycin group, the mTOR siRNA group, the combined treatment group,and the blank control group and the cisplatinum treatment group were served as the control group.The number of each group was five.After two weeks of the consecutive treatment,the tumors were removed and then the tumor volumes before and after treatment were measured.The in situ hybridization and the immunohistochemistry were used to detect the mRNA and protein expression of the mTOR.Results: ①Tumor volumes in nude mices can be reduced by individual treatment of rapamycin (F=185.00,P<0.001), or mTOR siRNA (F=199.01,P<0.001);there is an interaction between rapamycin and mTOR siRNA (F= 30.30,P<0.001),and when in combination, the tumor volumes in nude mices have a more significant decline.There are not statistically significant difference between the tumor volumes of nude mices after cisplatinum treatment and the ones after the combined treatment of rapamycin and mTOR siRNA (t=0.426,P=0.682).②The mTOR protein or mTOR mRNA expressions of human esophageal carcinoma xenografts in nude mices can be reduced by individual treatment of rapamycin (F=395.76,550.04,P<0.001), or mTOR siRNA (F=367.58,573.39), P<0.001); there is an interaction between rapamycin and mTOR siRNA (F=11.68,P=0.004;F=10.23,P=0.006), and when in combination, the mTOR protein or mTOR mRNA expressions have a more significant decline. There are not statistically significant difference between the mTOR protein(7.15±0.56) or mTOR mRNA(6.88±0.59) expressions of human esophageal carcinoma xenografts in nude mices after cisplatinum treatment and the ones after the combined treatment of rapamycin and mTOR siRNA (t=0.622,P=0.551;t=0.572,P=0.583).Conclusion:Both the mTOR siRNA and the rapamycin can inhibit the tumor growth, and downregulate the the mRNA and protein expression of the mTOR of human esophageal carcinoma xenografts in the nude mice. The effect is best when they are combined.

参考文献/References:

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备注/Memo

备注/Memo:
*河南省杰出青年科学基金资助项目074100510009;河南省科技攻关计划基金资助项目082102310011;河南省基础与前沿技术研究计划基金资助项目092300410016;郑州市科技创新团队基金资助项目 #通讯作者,男,1964年生,博士,教授,研究方向:肿瘤病理,Email:chenksh2002@yahoo.com.cn
更新日期/Last Update: 2010-05-14