缺氧微环境的形成是导致肝癌治疗失败的重要原因，缺氧诱导因子- 2α（HIF-2α）是缺氧下起关键作用的调控因子，但HIF-2α表达调控的机制尚不清楚。 我们前期在肝癌细胞中研究发现环氧合酶-2（COX-2）活性产物PGE2（前列腺素E2）可通过抑制 vHL(Von Hippel–Lindau) 表达抑制HIF-2α降解，亦可通过抑制细胞自噬激活抑制HIF-2α降解。 COX-2/PGE2通路可能是通过vHL途径与自噬途径共同调控HIF-2α的降解，但其分子调控机制尚不明确。本研究拟在缺氧环境下应用细胞培养、蛋白芯片、免疫印记、动物实验等技术，探讨COX-2/PGE2通路在此过程中的调控机制。本项目将为肝癌治疗药物的开发提供潜在的蛋白靶点及实验依据。

Formation of hypoxic microenvironment is an important reason for failure of hepatocellular carcinoma (HCC) therapy. Hypoxia-inducible factor-2α (HIF-2α) is a key mediator under the hypoxic state, but the mechanism that regulates its expression remains unknown. In our previous studies of HCC cells, we found that prostaglandin E2 (PGE2), the active product of cyclooxygenase-2 (COX-2), could inhibit the degeneration of HIF-2α by inhibiting the expression of Von Hippel–Lindau (vHL) and preventing autophagy. The COX-2/PGE2 pathway might regulate the degeneration of HIF-2α through the vHL and autophagy pathways, but the underlying molecular mechanisms are still unclear. Using techniques, such as cell culture, protein chips, immunoblotting and in vivo animal experiments, the present study will examine the role of COX-2/PGE2 pathway in this process under hypoxic conditions, which may provide potential protein targets and experimental evidence for the development of therapeutic agents against HCC.