携带siRNA-STAT3质粒的减毒沙门菌对小鼠移植性前列腺癌的治疗作用

J4 ›› 2010, Vol. 36 ›› Issue (3): 477-482.

携带siRNA-STAT3质粒的减毒沙门菌对小鼠移植性前列腺癌的治疗作用

刘喜东¹|周悦¹|周姝含², 王芳¹|曹群¹|周庆伟³,赵雪俭²

1.吉林大学药学院生物医学工程教研室|吉林长春 130021|2.吉林大学基础医学院病理生理学教研室, 吉林长春 130021|3.吉林大学再生医学科学研究所生物化学研究室|吉林长春 130021

收稿日期:2010-01-04 出版日期:2010-05-28 发布日期:2010-05-28
通讯作者: 周庆伟 (Tel:0431-85619386，E-mail: qingwei_zhou@yahoo.com) E-mail:qingwei_zhou@yahoo.com
作者简介:刘喜东(1981-),男,吉林省长春市人,医学硕士,主要从事抗肿瘤血管生成靶向研究。
基金资助:
吉林省科技厅科研基金资助课题 (200705383)

Therapeutic |effect of |attenuated salmonella carrying |siRNA-STAT3 |plasmid on transplanted |prostatic cancer in mice

LIU Xi-Dong¹, ZHOU Yue¹, ZHOU Shu-Han², WANG Fang¹, CAO Qun¹, ZHOU Qing-Wei³, ZHAO Xue-Jian²

1. Department of Biomedical Engineering, School of Pharmacy, Jilin University, Changchun 130021, China|2. Department of |Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China；3.Department of Biochemistry, Institute of Frontier Medical Sciences, Jilin University, Changchun 130021, China

Received:2010-01-04 Online:2010-05-28 Published:2010-05-28

摘要/Abstract

摘要：

目的：观察以减毒沙门菌携带siRNA-STAT3质粒对小鼠前列腺移植癌的治疗效果，阐明siRNA-STAT3诱导前列腺癌细胞凋亡的机制。方法：构建小鼠前列腺移植癌模型，随机分为Mock未治疗组、pGC-Si-Scramble组及pGC-Si-STAT3治疗组（将转化有siRNA-STAT3质粒的减毒沙门菌局部注射到模型构建成功的小鼠体内）。观察小鼠一般状态，记录肿瘤体积的变化，RT-PCR和Western boltting方法检测STAT3 及其下游基因Bcl-2、c-Myc、HIF-1、CyclinD1的 mRNA和蛋白表达水平，流式细胞术检测肿瘤细胞凋亡。结果：小鼠前列腺移植癌模型构建成功，pGC-Si-STAT3治疗组移植性前列腺癌瘤体生长受到明显抑制，肿瘤的质量和体积明显低于对照组（P<0.05）。流式细胞术检测，pGC-Si-STAT3治疗组、pGC-Si-Scramble组及Mock未治疗组肿瘤细胞早期凋亡率分别为（29.1±1.6）%、（14.7±1.4）%和（8.9±1.8）%，组间比较差异有显著性(P<0.05)。pGC-Si-STAT3治疗组肿瘤组织的STAT3 mRNA和蛋白表达明显降低，其下游基因Bcl-2、 c-Myc的mRNA及HIF-1、CyclinD1蛋白的表达水平均降低，与Mock未治疗组比较差异有显著性（P<0.05）。结论：以减毒沙门菌作为运载体携带siR
NA-STAT3质粒通过调控STAT3下游基因表达，诱导细胞凋亡，对小鼠移植性前列腺癌具有明显的抑瘤效果。

关键词: 前列腺肿瘤；减毒沙门氏菌；STAT3；RNA干涉

Abstract:

Abstract:Objective To observe the therapeutic effect of attenuated salmonella carrying siRNA-STAT3 plasmid on transplanted prostatic cancer in mice,and clarify the mechanism of siRNA-STAT3 of inducing apoptosis of prostatic cancer cells in mice. Methods The transplanted prostatic cancer models of mice were built,then the mice were randomly divided into Mock group, pGC-Si-Scramble group and pGC-Si-STAT3 group. The general status of the mice was observed and the changes of tumor volume were recorded.The expression levels of mRNA and protein of STAT3 and its downstream genes such as Bcl-2,c-Myc, HIF-1,cyclinD1 were analyzed with RT-PCR and THE Western blotting, and the apoptosis of tumor cells was detected with flow cytometry. Results The transplanted prostatic cancer models of the mice were built successfully.Compared with Mock group, the growth of tumor was suppressed obviously and the weights of tumors were lessened in pGC-Si-STAT3 group（P<0.05）.The result of flow cytometry revealed that the early apoptotic rates in pGC-Si-STAT3 group, pGC-Si-Scramble group and Mock group were （29.1±1.6）%,（14.7±1.4）%,and（8.9±1.8）%, respectively. Compared with Mock group, the mRNA and protein expression levels of STAT3 in pGC-Si-STAT3 group were singnificantly decreased, the mRNA expressions of the downtream genes, such as BcL-2,c-Myc were decreased, and the protein expression levels of HIF-1, cyclinD1 were also decreaaed（P<0.05）.Conclusion The attenuated salmonella carrying SiRNA-STAT3 can inhibit the growth of transplanted prostatic cancer in mice by regulating the expressions of STAT3 downtream genes and inducing the apoptosis of tumor cells.

Key words: prostatic neoplasms, attenuated salmonella, STAT3; , RNA interfere

中图分类号:

R737.25

刘喜东, 周悦, 周姝含, 王芳, 曹群, 周庆伟, 赵雪俭. 携带siRNA-STAT3质粒的减毒沙门菌对小鼠移植性前列腺癌的治疗作用[J]. J4, 2010, 36(3): 477-482.