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学科主题: 临床医学
题名:
The therapeutic and preventive effect of RRR-alpha-vitamin E succinate on prostate cancer via induction of insulin-like growth factor binding protein-3
作者: Yin, Yi; Ni, Jing; Chen, Ming; DiMaggio, Matthew A.; Guo, Yinglu; Yeh, Shuyuan
刊名: CLINICAL CANCER RESEARCH
发表日期: 2007-04-01
DOI: 10.1158/1078-0432.CCR-06-1217
卷: 13, 期:7, 页:2271-2280
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]: ATHYMIC NUDE-MICE ; FACTOR-I ; TRANSGENIC ADENOCARCINOMA ; FACTOR BINDING-PROTEIN-3 ; TRIGGERED APOPTOSIS ; ANDROGEN RECEPTOR ; RETINOIC ACID ; TUMOR-GROWTH ; LUNG-CANCER ; CELL-GROWTH
英文摘要:

Purpose: Insulin-like growth factor binding protein-3 (IGFBP-3) is a well-known antiproliferative and proapoptotic molecule in prostate cancer, suggesting that targeting IGFBP-3 might produce clinical benefits. In prostate cancer cells, RRR-alpha-vitamin E succinate (VES) inhibits cell proliferation and induces apoptosis, yet the mechanisms remain to be elucidated. We hypothesize that the protective effects of VES in prostate cancer are mediated by IGFBP-3 up-regulation. Using prostate cancer models, the involvement of IGFBP-3 in the anticancer effect of VES was investigated.

Experimental Design: IGFBP-3 mRNA and protein were determined by real-time PCR and Western blotting in prostate cancer cells, xenografted tumors of nude mice, and prostate tumors of transgenic adenocarcinoma mouse prostate (TRAMP) mice. The serum levels of IGFBP-3 were assessed by ELISA. The importance of IGFBP-3 in VES-mediated antitumor effects was confirmed by small interfering RNA knockdown strategy.

Results: We found that VES induced IGFBP-3 mRNA and protein levels in human prostate cancer cell lines. Knockdown of IGFBP-3 by small interfering RNA attenuated VES-induced IGFBP-3 expression and VES-mediated antiproliferative and proapoptotic functions. Furthermore, administration of VES resulted in a significant therapeutic effect on LNCaP and PC3 xenografts and a preventive effect on tumorigenic progression in the TRAMP model without overt toxicity. Notably, the therapeutic and preventive efficacy of VES correlated with increased accumulation of IGFBP-3 in mouse serum as well as in the xenograft tumors and TRAMP prostate samples. Consequently, reduced proliferation and induced apoptosis were witnessed.

Conclusions: VES mediates its therapeutic and preventive effects against prostate cancer at least partially through up-regulating IGFBP-3, which inhibits cell proliferation and promotes cell apoptosis.

语种: 英语
WOS记录号: WOS:000245660800041
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55043
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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作者单位: 1.Univ Rochester, Dept Urol, George Whipple Lab Canc Res, Rochester, NY 14642 USA
2.Univ Rochester, Dept Pathol, George Whipple Lab Canc Res, Rochester, NY 14627 USA
3.Peking Univ, Inst Urol, Peking Univ Hosp 1, Beijing 100871, Peoples R China

Recommended Citation:
Yin, Yi,Ni, Jing,Chen, Ming,et al. The therapeutic and preventive effect of RRR-alpha-vitamin E succinate on prostate cancer via induction of insulin-like growth factor binding protein-3[J]. CLINICAL CANCER RESEARCH,2007,13(7):2271-2280.
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