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IR@PKUHSC  > 北京大学第一临床医学院  > 消化内科  > 期刊论文
学科主题: 临床医学
题名:
Adenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer
作者: Dai, Yun2,3,4; Qiao, Liang1,3,4,7; Chan, Kwok Wah5; Yang, Mo6; Ye, Jieyu6; Zhang, Rongxin3,4; Ma, Juan3,4; Zou, Bing3,4; Lam, Colin S. C.3,4; Wang, Jide3,4; Pang, Roberta3,4; Tan, Victoria P. Y.3,4; Lan, H. Y.3,4; Wong, Benjamin C. Y.3,4
刊名: MOLECULAR CANCER THERAPEUTICS
发表日期: 2009-09-01
DOI: 10.1158/1535-7163.MCT-09-0509
卷: 8, 期:9, 页:2762-2770
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: HEPATOCELLULAR-CARCINOMA CELLS ; TRAIL-INDUCED APOPTOSIS ; SMALL INTERFERING RNA ; NF-KAPPA-B ; XIAP EXPRESSION ; IN-VIVO ; GENE ; GROWTH ; VITRO ; SENSITIVITY
英文摘要:

Our previous studies and those of others have indicated that X-linked inhibitor of apoptosis protein (XIAP) holds promise as a target gene in colon cancer gene therapy. In this study, we constructed an adenoviral vector to deliver small hairpin RNA (shRNA) against XIAP (XIAP-shRNA) into colon cancer cells and tested its therapeutic efficacy in vitro and in vivo. We first confirmed an overexpression of XIAP in colon cancer cells and human cancer tissues. We then designed XIAP-small interfering RNA (siRNA) and confirmed the knockdown effect of these siRNAs in colon cancer cells. The sequences of the effective siRNAs were converted into shRNA and then packed into replication-deficient adenoviral vectors using BLOCK-iT Adenoviral RNAi Expression System to generate Adv-XIAP-shRNA. Infection of HT29 and HCT116 cells with Adv-XIAP-shRNA led to enhanced caspase-3 activity, which was associated with increased apoptosis and reduced cell proliferation. The therapeutic effect of Adv-XIAP-shRNA was then tested in xenograft tumors in nude mice. We showed that treatment of the xenograft tumors derived from HCT116 cells with Adv-XIAP-shRNA resulted in a retardation of tumor growth, which was associated with enhanced apoptosis, increased caspase-3 activity, and reduced expression of proliferating cell nuclear antigen in the tumor tissues. Treatment of xenograft tumors with Adv-XIAP-shRNA did not affect the expressions of inflammatory cytokines in tumor-bearing mice. Thus, Adv-XIAP-shRNA-mediated down-regulation of XIAP exerts a therapeutic effect in colon cancer by promoting apoptosis and inhibiting proliferation of colon cancer cells, and the antitumor effect of Adv-XIAP-shRNA was unlikely to be related to virus-induced immune response. [Mol Cancer Ther 2009;8(9):2762-70]

语种: 英语
WOS记录号: WOS:000269968900029
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60861
Appears in Collections:北京大学第一临床医学院_消化内科_期刊论文

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作者单位: 1.Univ Sydney, Dept Gastroenterol & Hepatol, Westmead Hosp, Westmead, NSW 2145, Australia
2.Peking Univ, Dept Gastroenterol, Hosp 1, Beijing 100871, Peoples R China
3.Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China
4.Univ Hong Kong, Ctr Canc Res, Hong Kong, Hong Kong, Peoples R China
5.Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China
6.Univ Hong Kong, Dept Pediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China
7.Univ Sydney, Storr Liver Unit, Westmead Hosp, Westmead, NSW 2145, Australia

Recommended Citation:
Dai, Yun,Qiao, Liang,Chan, Kwok Wah,et al. Adenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer[J]. MOLECULAR CANCER THERAPEUTICS,2009,8(9):2762-2770.
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