The Kringle 1 domain of hepatocyte growth factor has antiangiogenic and antitumor cell effects on hepatocellular carcinoma
文献类型：期刊论文
| 作者 | Zan, S; Zhen, FY; Yi, G; Ji, CL; Hai, XC; Ching, CL; Poon, RTP; Fan, ST; Luk, JM; Kong, HS |
| 刊名 | CANCER RESEARCH
 |
| 出版日期 | 2008 |
| 卷号 | 68期号:2页码:404-414 |
| 通讯作者 | Lin, MCM (reprint author), Univ Hong Kong, Inst Mol Biol, Dept Chem, 8-F Kadoorie Biol Sci Bldg,Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China.,mcllin@hkusuahku.hk |
| 英文摘要 | The kringle I domain of human hepatocyte growth factor (HGFK1) was previously shown to inhibit bovine aortic endothelial cell proliferation, suggesting that it might be an antiangiogenic molecule. Here, we evaluated the in vivo efficacy of a recombinant adenoassociated virus carrying HGFK1 (rAAV-HGFK1) for the treatment of hepatocellular carcinoma (HCC) in a rat orthotopic HCC model and explored its molecular mechanisms in vitro in both endothelial and tumor cells. We first showed that rAAV-HGFK1 treatment significantly prolonged the survival time of rats transplanted with tumor cells. Treatment with rAAV-HGFK1 inhibited tumor growth, decreased tumor microvessel density, and completely prevented intrahepatic, lung, and peritoneal metastasis in this in vivo model. In vitro, rAAV-HGFK1 exhibited both antiangiogenic and antitumor cell effects, inhibiting the proliferation of both murine microvascular endothelial cells (MEC) and tumor cells, and inducing apoptosis and GO-G, phase arrest in these cells. To our surprise, rAAV-HGFK1 did not act through the hepatocyte growth factor/hepatocyte growth factor receptor pathway. Instead, it worked mainly through epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) signaling, with more minor contributions from vascular endothelial growth factor/vascular endothelial growth factor receptor and 0 fibroblast growth factor (bFGF)/beta fibroblast growth factor receptor (bFGFR) signaling. In both MECs and tumor cells, rAAV-HGFK1 acted through two pathways downstream of EGFR, namely inhibition of extracellular signal-regulated kinase activation and stimulation of p38 mitogen-activated protein kinase/c-jun-NH2-kinase activation. These results suggest for the first time that HGFK1 exerts both antiangiogenic and antitumor cell activities mainly through EGF/EGFR signaling, and may thus be considered as a novel therapeutic strategy for the treatment of HCC. |
| 学科主题 | Oncology |
| 类目[WOS] | Oncology |
| 关键词[WOS] | CANCER GENE-THERAPY ; PHASE-II ; ANGIOGENESIS ; VECTOR ; ANGIOSTATIN ; COMBINATION ; CARBOPLATIN ; EXPRESSION ; ENDOSTATIN ; SURVIVAL |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000252503800011 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1348]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zan, S,Zhen, FY,Yi, G,et al. The Kringle 1 domain of hepatocyte growth factor has antiangiogenic and antitumor cell effects on hepatocellular carcinoma[J]. CANCER RESEARCH,2008,68(2):404-414. |
| APA | Zan, S.,Zhen, FY.,Yi, G.,Ji, CL.,Hai, XC.,...&Lin, MCM.(2008).The Kringle 1 domain of hepatocyte growth factor has antiangiogenic and antitumor cell effects on hepatocellular carcinoma.CANCER RESEARCH,68(2),404-414. |
| MLA | Zan, S,et al."The Kringle 1 domain of hepatocyte growth factor has antiangiogenic and antitumor cell effects on hepatocellular carcinoma".CANCER RESEARCH 68.2(2008):404-414. |
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