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学科主题临床医学
Loss of XIAP sensitizes rosiglitazone-induced growth inhibition of colon cancer in vivo
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
2008-06-15
DOI10.1002/ijc.23443
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
引用统计
被引频次:27[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/400002259/55485
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, 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
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GB/T 7714
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.
APA Dai, Yun.,Qiao, Liang.,Chan, Kwok Wah.,Zou, Bing.,Ma, Juan.,...&Wong, Benjamin C. Y..(2008).Loss of XIAP sensitizes rosiglitazone-induced growth inhibition of colon cancer in vivo.INTERNATIONAL JOURNAL OF CANCER,122(12),2858-2863.
MLA Dai, Yun,et al."Loss of XIAP sensitizes rosiglitazone-induced growth inhibition of colon cancer in vivo".INTERNATIONAL JOURNAL OF CANCER 122.12(2008):2858-2863.
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