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学科主题: 临床医学
题名:
Loss of XIAP sensitizes rosiglitazone-induced growth inhibition of colon cancer in vivo
作者: Dai, Yun1,2; Qiao, Liang; Chan, Kwok Wah3; Zou, Bing1; Ma, Juan1; Lan, Hui Y.1; Gu, Qing1; Li, Zesong1; Wang, Yan2; Wong, Benny L. W.1; Wong, Benjamin C. Y.1
关键词: colon cancer ; PPAR gamma ; rosiglitazone ; in vivo ; therapy
刊名: INTERNATIONAL JOURNAL OF CANCER
发表日期: 2008-06-15
DOI: 10.1002/ijc.23443
卷: 122, 期:12, 页:2858-2863
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]: ACTIVATED-RECEPTOR-GAMMA ; NF-KAPPA-B ; PPAR-GAMMA ; INDUCED APOPTOSIS ; BREAST-CANCER ; CELLS ; DIFFERENTIATION ; LIGANDS ; CARCINOGENESIS ; CARCINOMA
英文摘要:

Ligands for peroxisome proliferator-activated receptor gamma (PPAR gamma) possess anticancer properties. However, the efficacy of PPAR gamma ligands varies in different cancers. In colon cancer, the role of PPAR gamma and its ligands is controversial. We recently showed that downregulation of X-linked inhibitor of apoptosis protein (XIAP) could sensitize colon cancer cells to troglitazone, and 15-deoxy-D12,14-prostaglandin J2 (15-PGJ2) induced cell killing. In our study, we aimed to examine whether rosiglitazone, another more clinically relevant PPAR gamma ligand, has any synergistic anticancer effect with XIAP downregulation in colon cancer. Human colon cancer cell lines HCT116-XIAP(+/+) cells and HCT116-XIAP(-/-) cells were treated with various concentrations of rosiglitazone. The effects of rosiglitazone on cell proliferation, apoptosis and growth of xenograft colon cancers were studied. Rosiglilazone barely suppressed the growth and only very weakly induced apoptosis in HCT116 cells in vitro. Loss of XIAP did not sensitize HCT116 cells to rosiglitazone-induced growth inhibition or apoptosis. In vivo studies revealed that rosiglitazone strongly suppressed the growth of xenograft colon cancer, especially tumors derived from HCT116-XIAP(-/-) cells. The rosiglitazone-treated tumor had reduced expression of ki-67 and lowered mitotic rate. Downregulation of XIAP was associated with an impaired activation of PPAR gamma by its ligand. Rosiglilazone induced marked upregulation of PTEN in HCT116-XIAP(-/-) cells, as well as in xenograft tumors derived from HCT116-XIAP(-/-) cells. We concluded that rosiglitazone significantly suppresses the growth of xenograft colon cancer, and downregulation of XIAP sensitizes the xenograft tumors to rosiglitazone-induced tumor suppression in vivo via upregulation of PTEN. (C) 2008 Wiley-Liss, Inc.

语种: 英语
WOS记录号: WOS:000256713800027
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55485
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.Peking Univ, Hosp 1, Dept Gastroenterol, Beijing 100871, Peoples R China
3.Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China

Recommended Citation:
Dai, Yun,Qiao, Liang,Chan, Kwok Wah,et al. Loss of XIAP sensitizes rosiglitazone-induced growth inhibition of colon cancer in vivo[J]. INTERNATIONAL JOURNAL OF CANCER,2008,122(12):2858-2863.
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