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Effects of transferred NK4 gene on proliferation, migration,invasion and apoptosis of human prostate cancer DU145 cells

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Yue Dan 1   Wang Yong 2   Ma Ping 1   Li Yinyan 3   Chen Hong 1   Wang Ping 2   Ren Changshan 1 *  
文摘 We investigated the ability of NK4, an antagonist of human hepatocyte growth factor (HGF), to inhibit the influence of HGF on proliferation, migration, invasion and apoptosis of human prostate cancer cells. Expression vector pBudCE4.1-EGFP-NK4 containing NK4 cDNA was used to transfect human prostate cancer DU145 cells, and the effects of the autocrine NK4 on tumor cell proliferation, migration, invasion and apoptosis were assessed in vitro. In vivo, we subcutaneously implanted DU145 cells, mock-transfected clone (DU145/empty vector) cells and NK4transfected clone (DU145/NK4) cells into nude mice, and then evaluated tumor growth, cell proliferation and cell apoptosis in vivo. We found that DU145/NK4 cells expressed NK4 protein. In the in vitro study, autocrine NK4 attenuated the HGF-induced tumor cell proliferation, migration and invasion, and stimulated apoptosis. Furthermore, autocrine NK4 effectively inhibited the HGF-induced phosphorylation of c-Met, extracellular signal-regulated kinase-1 (ERK1). and protein kinase B 1/2 (Aktl/2). Histological examination revealed that autocrine NK4 inhibited proliferation and accelerated apoptosis of prostate cancer cells. These results show that genetic modification of DU145 cells with NK4 cDNA yields a significant effect on their proliferation, migration, invasion and apoptosis. Molecular targeting of HGF/c-Met by NK4 could be applied as a novel therapeutic approach to prostate cancer.
来源 Asian Journal of Andrology ,2010,12(3):381-389 【核心库】
DOI 10.1038/aja.2010.22
关键词 hepatocyte growth factor ; human prostate cancer ; NK4 ; DU145 cells
地址

1. Cancer Research Institute, First Affiliated Hospital, China Medical University, Shenyang, 110001  

2. Department of Urology, Fourth Affiliated Hospital, China Medical University, Shenyang, 110032  

3. Department of Ultrasound, First Affiliated Hospital, China Medical University, Shenyang, 110001

语种 英文
文献类型 研究性论文
ISSN 1008-682X
学科 临床医学
文献收藏号 CSCD:3891332

参考文献 共 18 共1页

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引证文献 6

1 Wang Yong The role of TRPC6 in HGF-induced cell proliferation of humanprostate cancer DU145 and PC3 cells Asian Journal of Andrology,2010,12(6):841-852
被引 1

2 匡文斌 重组腺病毒Ad5-hNK4-EGFP的构建与鉴定 中国生物制品学杂志,2012,25(6):676-681
被引 3

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