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Down-regulation of X-linked inhibitor of apoptosis synergistically enhanced peroxisome proliferator-activated receptor gamma ligand-induced growth inhibition in colon cancer
Oiao, Liang; Dai, Yun3; Gu, Oing3; Chan, Kwok Wah2; Zou, Bing; Ma, Juan; Wang, Jide; Lan, Hui Y.; Wong, Benjamin C. Y.1
刊名MOLECULAR CANCER THERAPEUTICS
2008-07-01
DOI10.1158/1535-7163.MCT-08-0326
7期:7页:2203-2211
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 ; PPAR-GAMMA ; COLORECTAL-CANCER ; IN-VIVO ; THERAPEUTIC TARGET ; ENDOTHELIAL-CELLS ; XIAP EXPRESSION ; TUMOR-GROWTH ; NUDE-MICE ; PHASE-II
英文摘要

We found previously that X-linked inhibitor of apoptosis protein (XIAP), a potent endogenous inhibitor of apoptosis, is overexpressed in colon cancer. Ligand-induced activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) has been shown to exert proapoptotic and antiproliferative effects in many cancer cell types. However, neither XIAP down-regulation alone nor monotherapy using PPAR gamma ligands is potent enough to control colon cancer. We explored whether XIAP inhibition and PPARy activation offer a synergistic anticancer effect in colon cancer. HCT116-XIAP(+/+) and HCT116-XIAP(-/-) cells were treated with troglitazone or 15-deoxy-Delta(12,14)- prostaglandin J(2) (15-PGJ(2)). Cell growth and apoptosis were measured. Nude mice were s.c. inoculated with HCT116 cells with or without oral troglitazone. Tumor growth, angiogenesis, and apoptosis were measured. Troglitazone- and 15-PGJ(2)-induced growth inhibition and apoptosis were more prominent in HCT116-XIAP(-/-) cells. Troglitazone- and 15-PGJ2-induced apoptosis correlated with enhanced cleavage of caspases and poly(ADPribose) polymerase, which were more profound in HCT116-XIAP(-/-) cells. Pretreatment of cells with XIAP inhibitor 1396-12 also sensitized HCT116-XIAP(+/+) cells to PPAR gamma ligand-induced apoptosis. Troglitazone significantly retarded the growth of xenograft tumors, more significantly so in HCT116-XIAP(-/-) cell-derived tumors. Reduction of tumor size was associated with reduced expression of Ki-67, vascular endothelial growth factor, and CD31 as well as increased apoptosis. Loss of XIAP significantly sensitized colorectal cancer cells to PPAR gamma ligand-induced apoptosis and inhibition of cell proliferation. Thus, simultaneous inhibition of XIAP and activation of PPAR gamma may have a synergistic antitumor effect against colon cancer.

语种英语
WOS记录号WOS:000257964100047
引用统计
被引频次:20[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/400002259/59882
专题北京大学第一临床医学院_消化科
作者单位1.Univ Hong Kong, Dept Med, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China
2.Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China
3.Peking Univ, Hosp 1, Dept Gastroenterol, Beijing 100871, Peoples R China
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GB/T 7714
Oiao, Liang,Dai, Yun,Gu, Oing,et al. Down-regulation of X-linked inhibitor of apoptosis synergistically enhanced peroxisome proliferator-activated receptor gamma ligand-induced growth inhibition in colon cancer[J]. MOLECULAR CANCER THERAPEUTICS,2008,7(7):2203-2211.
APA Oiao, Liang.,Dai, Yun.,Gu, Oing.,Chan, Kwok Wah.,Zou, Bing.,...&Wong, Benjamin C. Y..(2008).Down-regulation of X-linked inhibitor of apoptosis synergistically enhanced peroxisome proliferator-activated receptor gamma ligand-induced growth inhibition in colon cancer.MOLECULAR CANCER THERAPEUTICS,7(7),2203-2211.
MLA Oiao, Liang,et al."Down-regulation of X-linked inhibitor of apoptosis synergistically enhanced peroxisome proliferator-activated receptor gamma ligand-induced growth inhibition in colon cancer".MOLECULAR CANCER THERAPEUTICS 7.7(2008):2203-2211.
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