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学科主题: 临床医学
题名:
Peroxisome Proliferator-Activated Receptor-gamma Contributes to the Inhibitory Effects of Embelin on Colon Carcinogenesis
作者: Dai, Yun1,4; Qiao, Liang1; Chan, Kwok Wah2; Yang, Mo3; Ye, Jieyu3; Ma, Juan1; Zou, Bing1; Gu, Qing1; Wang, Jide1; Pang, Roberta1; Lan, H. Y.1; Wong, Benjamin C. Y.1
刊名: CANCER RESEARCH
发表日期: 2009-06-01
DOI: 10.1158/0008-5472.CAN-08-4754
卷: 69, 期:11, 页:4776-4783
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]: NF-KAPPA-B ; NITROSODIETHYLAMINE/PHENOBARBITAL-INDUCED HEPATOCARCINOGENESIS ; COLORECTAL-CANCER CELLS ; PPAR-GAMMA ; HEPATOCELLULAR-CARCINOMA ; APOPTOSIS PROTEIN ; LINKED INHIBITOR ; WISTAR RATS ; IN-VIVO ; XIAP
英文摘要:

Down-regulation of XIAP (X-linked inhibitor of apoptosis protein) sensitizes colon cancer cells to the anticancer effect of peroxisome proliferator-activated receptor-gamma (PPAR gamma) ligands in mice. The aims of this study were to evaluate the effect of embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone), an antagonist of XIAP, on colon cancer, with a particular focus on whether PPAR gamma is required for embelin to exert its effect. A dominant-negative PPAR gamma was used to antagonize endogenous PPAR gamma in HCT116 cells. Cells were treated with or without embelin. Cell proliferation, apoptosis, and nuclear factor-kappa B (NF-kappa B) activity were measured. For in vivo studies, 1,2-dimethylhydrazine dihydrochloride (DMH) was s.c. injected to induce colon cancer in PPAR gamma(+/+) and PPAR gamma(+/-) mice. Mice were fed embelin daily for 10 days before DMH injection, and continued for 30 more weeks. Embelin inhibited proliferation and induced apoptosis in HCT116 cells with marked up-regulation of PPAR gamma. In addition, embelin significantly inhibited the expressions of survivin, cyclin D1, and c-Myc. These effects were partially dependent on PPAR gamma. PPAR gamma(+/-) mice were more susceptible to DMH-induced colon carcinogenesis than PPAR gamma(+/+) mice, and embelin significantly reduced the incidence of colon cancer in PPAR gamma(+/+) mice but not in PPAR gamma(+/-) mice. Embelin inhibited NF-kappa B activity in PPAR gamma(+/+) mice but marginally so in PPAR gamma(+/-) mice. Thus, reduced expression of PPAR gamma significantly sensitizes colonic tissues to the carcinogenic effect of DMH. Embelin inhibits chemical carcinogen-induced colon carcinogenesis, but this effect is partially dependent on the presence of functional PPAR gamma, indicating that PPAR gamma is a necessary signaling pathway involved in the antitumor activity of norma organisms. [Cancer Res 2009;69(11):4776-83]

语种: 英语
所属项目编号: 10206827.49710.20600.302.01
项目资助者: Simon K.Y. Lee endowed professorship Research Fund ; Gordon Chiu Stomach Cancer Research Fund ; Outstanding Researcher Award Fund of the University of Hong Kong, Hong Kong ; University of Hong Kong Seed Funding
WOS记录号: WOS:000266755000030
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61670
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 Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China
2.Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China
3.Univ Hong Kong, Dept Pediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China
4.Peking Univ, Hosp 1, Dept Gastroenterol, Beijing 100871, Peoples R China

Recommended Citation:
Dai, Yun,Qiao, Liang,Chan, Kwok Wah,et al. Peroxisome Proliferator-Activated Receptor-gamma Contributes to the Inhibitory Effects of Embelin on Colon Carcinogenesis[J]. CANCER RESEARCH,2009,69(11):4776-4783.
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