Department of Hepatobiliary Surgery, 302 Hospital of PLA, Beijing 100039, PR China.
Oncol Rep. 2013 Jan;29(1):362-70. doi: 10.3892/or.2012.2103. Epub 2012 Oct 23.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide; however, the prognosis of HCC patients remains poor. This poor prognosis is mainly attributed to the high rate of intrahepatic and distant metastasis. HCC often occurs in a hypoxic environment and hypoxia can activate metastatic programs, ultimately leading to tumor recurrence or metastasis. Thus, the discovery and subsequent development of novel agents to block HCC invasion and migration are the primary objectives of hepatic cancer research. The Notch1 signaling pathway might be involved in hypoxia-induced carcinoma metastasis. However, the mechanisms by which Notch1 mediates cell metastasis, particularly in hepatocellular carcinoma, are not yet entirely clear. The results of the present study show that hypoxia increases the invasion and migration capacities of different HCC cells. Activation of the Notch1 signaling pathway contributes to hypoxia-induced invasion and migration in HCC cells. The activated Notch1 signaling pathway can regulate Snail/E-cadherin through cyclooxygenase-2 (COX-2) under hypoxic conditions. The above results suggest that the Notch1/COX-2/Snail/E-cadherin pathway is possibly associated with hypoxia-induced invasion and migration in HCC cells. Thus, targeting Notch1 may be useful for devising novel preventive and therapeutic strategies for HCC.
肝细胞癌 (HCC) 是全球最常见的恶性肿瘤之一；然而，HCC 患者的预后仍然很差。这种不良预后主要归因于肝内和远处转移的高发生率。HCC 常发生在缺氧环境中，缺氧可激活转移程序，最终导致肿瘤复发或转移。因此，发现和随后开发新型药物来阻断 HCC 的侵袭和迁移是肝癌研究的主要目标。Notch1 信号通路可能参与缺氧诱导的癌症转移。然而，Notch1 介导细胞转移的机制，特别是在肝细胞癌中，尚不完全清楚。本研究结果表明，缺氧增加了不同 HCC 细胞的侵袭和迁移能力。Notch1 信号通路的激活有助于缺氧诱导的 HCC 细胞侵袭和迁移。在缺氧条件下，激活的 Notch1 信号通路可以通过环氧化酶-2 (COX-2) 调节 Snail/E-钙黏蛋白。上述结果表明，Notch1/COX-2/Snail/E-钙黏蛋白通路可能与 HCC 细胞缺氧诱导的侵袭和迁移有关。因此，靶向 Notch1 可能有助于制定 HCC 的新型预防和治疗策略。
