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Volume 12, Issue 3 (May 2010) 12, 381–389; 10.1038/aja.2010.22

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

Dan Yue1, Yong Wang2, Ping Ma1, Yin-Yan Li3, Hong Chen1, Ping Wang2 and Chang-Shan Ren1

1 Cancer Research Institute, First Affiliated Hospital, China Medical University, Shenyang 110001, China
2 Department of Urology, Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China
3 Department of Ultrasound, First Affiliated Hospital, China Medical University, Shenyang 110001, China

Correspondence: Dr Chang-Shan Ren,csrencmu@yahoo.com.cn; Dr Ping Wang, cmu4h-wp@126.com

Received 12 September 2009; Revised 16 November 2009; Accepted 16 March 2010; Published online 19 April 2010.


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 NK4-transfected 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 (Akt1/2). 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.

Keywords: hepatocyte growth factor; human prostate cancer; NK4; DU145 cells

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