|Tumor suppressor gene RBM5 delivered by attenuated Salmonella inhibits lung adenocarcinoma through diverse apoptotic signaling pathways|
|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|
|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|
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.
|项目编号||81071919 ; 30971315 ; 201015169|
|资助机构||National Natural Science Foundation of China ; Provincial Natural Science Foundation of Jilin|
|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
|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.|
|APA||Shao, Chen,Yang, Baoxue,Zhao, Lijing,Wang, Song,Zhang, Jie,&Wang, Ke.(2013).Tumor suppressor gene RBM5 delivered by attenuated Salmonella inhibits lung adenocarcinoma through diverse apoptotic signaling pathways.WORLD JOURNAL OF SURGICAL ONCOLOGY,11.|
|MLA||Shao, Chen,et al."Tumor suppressor gene RBM5 delivered by attenuated Salmonella inhibits lung adenocarcinoma through diverse apoptotic signaling pathways".WORLD JOURNAL OF SURGICAL ONCOLOGY 11(2013).|
|Tumor suppressor gen（1103KB）||期刊论文||出版稿||开放获取||CC BY-NC-SA||浏览 请求全文|