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学科主题临床医学
Adenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer
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
2009-09-01
DOI10.1158/1535-7163.MCT-09-0509
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
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被引频次:19[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60861
专题北京大学第一临床医学院_消化科
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
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GB/T 7714
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.
APA Dai, Yun.,Qiao, Liang.,Chan, Kwok Wah.,Yang, Mo.,Ye, Jieyu.,...&Wong, Benjamin C. Y..(2009).Adenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer.MOLECULAR CANCER THERAPEUTICS,8(9),2762-2770.
MLA Dai, Yun,et al."Adenovirus-mediated down-regulation of X-linked inhibitor of apoptosis protein inhibits colon cancer".MOLECULAR CANCER THERAPEUTICS 8.9(2009):2762-2770.
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