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学科主题: 基础医学
题名:
Tumor suppressor gene RBM5 delivered by attenuated Salmonella inhibits lung adenocarcinoma through diverse apoptotic signaling pathways
作者: Shao, Chen1; Yang, Baoxue4; Zhao, Lijing2,3; Wang, Song5; Zhang, Jie1; Wang, Ke1
关键词: RBM5 ; Lung adenocarcinoma ; Apoptosis ; A549 ; Xenograft mice model ; Attenuated Salmonella
刊名: WORLD JOURNAL OF SURGICAL ONCOLOGY
发表日期: 2013-05-31
DOI: 10.1186/1477-7819-11-123
卷: 11
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Surgery
研究领域[WOS]: Oncology ; Surgery
关键词[WOS]: HUMAN-CHROMOSOME 3P21.3 ; IN-VIVO ; CANCER CELLS ; CD95-MEDIATED APOPTOSIS ; HOMOZYGOUS DELETION ; DOWN-REGULATION ; SOLID TUMORS ; GROWTH ; RNA ; EXPRESSION
英文摘要:

Background: RBM5 (RNA-binding motif protein 5, also named H37/LUCA-15) gene from chromosome 3p21.3 has been demonstrated to be a tumor suppressor. Current researches in vitro confirm that RBM5 can suppress the growth of lung adenocarcinoma cells by inducing apoptosis. There is still no effective model in vivo, however, that thoroughly investigates the effect and molecular mechanism of RBM5 on lung adenocarcinoma.

Method: We established the transplanted tumor model on BALB/c nude mice using the A549 cell line. The mice were treated with the recombinant plasmids carried by attenuated Salmonella to induce the overexpression of RBM5 in tumor tissues. RBM5 overexpression was confirmed by immunohistochemistry staining. H&E staining was performed to observe the histological performance on plasmids-treated A549 xenografts. Apoptosis was assessed by TUNEL staining with a TUNEL detection kit. Apoptosis-regulated genes were detected by Western blot.

Results: We successful established the lung adenocarcinoma animal model in vivo. The growth of tumor xenografts was significantly retarded on the mice treated with pcDNA3.1-RBM5 carried by attenuated Salmonella compared to that on mice treated with pcDNA3.1. Overexpression of RBM5 enhanced the apoptosis in tumor xenografts. Furthermore, the expression of Bcl-2 protein was decreased significantly, while the expression of BAX, TNF-alpha, cleaved caspase-3, cleaved caspase-8, cleaved caspase-9 and cleaved PARP proteins was significantly increased in the pcDNA3.1-RBM5-treated mice as compared to that in the control mice.

Conclusions: In this study, we established a novel animal model to determine RBM5 function in vivo, and concluded that RBM5 inhibited tumor growth in mice by inducing apoptosis. The study suggests that although RBM5′s involvement in the death receptor-mediated apoptotic pathway is still to be investigated, RBM5-mediated growth suppression, at least in part, employs regulation of the mitochondrial apoptotic pathways.

语种: 英语
所属项目编号: 81071919 ; 30971315 ; 201015169
项目资助者: National Natural Science Foundation of China ; Provincial Natural Science Foundation of Jilin
WOS记录号: WOS:000319982600001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63746
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Jilin Univ, Dept Resp Med, Affiliated Hosp 2, Changchun 130041, Jilin, Peoples R China
2.Jilin Univ, China Japan Union Hosp, Dept Digest Med, Changchun 130033, Jilin, Peoples R China
3.Jilin Univ, Norman Bethune Coll Med, Dept Pathophysiol, Changchun 130021, Jilin, Peoples R China
4.Peking Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing 100191, Peoples R China
5.Jilin Univ, Dept Urinary Surg, Affiliated Hosp 1, Changchun 130041, Jilin, Peoples R China

Recommended Citation:
Shao, Chen,Yang, Baoxue,Zhao, Lijing,et al. Tumor suppressor gene RBM5 delivered by attenuated Salmonella inhibits lung adenocarcinoma through diverse apoptotic signaling pathways[J]. WORLD JOURNAL OF SURGICAL ONCOLOGY,2013,11.
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