Influence of hepatic artery occlusion on tumor growth and metastatic potential in a human orthotopic hepatoma nude mouse model: Relevance of epithelial-mesenchymal transition
Influence of hepatic artery occlusion on tumor growth and metastatic potential in a human orthotopic hepatoma nude mouse model: Relevance of epithelial-mesenchymal transition
复制标题
肝动脉闭塞对人原位肝癌裸鼠模型肿瘤生长和转移潜能的影响：上皮间质转化的相关性
DOI：
10.1111/j.1349-7006.2009.01363.x
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发表时间：
2010-01-01
期刊：
影响因子：
5.7
通讯作者：
Tang, Zhao-You
中科院分区：
文献类型：
--
作者：
Liu, Liang;Ren, Zheng-Gang;Tang, Zhao-You
肝动脉结扎（HAL）、经动脉栓塞（TAE）和经动脉化疗栓塞（TACE）已成为不可切除的肝细胞癌（HCC）的治疗选择。阻断肿瘤血供是这些治疗措施的重要机制之一。在这里，我们将HAL引入转移性人肝癌原位裸鼠模型（使用MHCC 97 L和HepG 2细胞系），以检查肝血流阻断对肝肿瘤细胞转移潜能的影响，并研究这些影响的机制。我们的研究结果表明，HAL抑制肿瘤生长，但伴随着引起肿瘤的适应和进展，增加了侵袭和远处转移的可能性。HAL的潜在促侵袭机制似乎与缺氧引起的肿瘤内缺氧和上皮-间质转化（EMT）增强有关。这与体外培养的MHCC 97 L和HepG 2细胞对缺氧的反应是雅阁的。磷脂酰肌醇3-激酶（PI 3 K）抑制剂LY 294002可通过抑制肝癌细胞EMT而增强HAL的治疗作用。它可能是有用的机制为基础的联合治疗，以提高初始的抗肿瘤反应的发展。（Cancer Sci 2009）。
Hepatic artery ligation (HAL), transarterial embolization (TAE), and transarterial chemoembolization (TACE) have been treatment choices for unresectable hepatocellular carcinoma (HCC). Obstruction of tumor blood supply is one of the most important mechanisms of these therapeutics measures. Here we introduced HAL into a metastatic human HCC orthotopic nude mouse model (using MHCC97L and HepG2 cell lines) to examine the effects of hepatic blood flow obstruction on the metastatic potential of hepatic tumor cells, and to investigate the mechanisms underlying these effects. Our results indicated that HAL inhibited tumor growth but concomitantly elicited tumor adaptation and progression, with increased potential for invasion and distant metastases. The underlying proinvasive mechanism of HAL appeared to be associated with enhanced intratumoral hypoxia and epithelial-mesenchymal transition (EMT) due to hypoxia. This was in accord with the in vitro response of MHCC97L and HepG2 cells to hypoxia. The therapeutic effects of HAL could be enhanced by the phosphatidyl inositol 3-kinase (PI3K) inhibitor LY294002, through arrest of EMT in hepatic tumor cells. It could be useful in the development of mechanism-based combination therapies to enhance the initial antitumor response. (Cancer Sci 2009).