Inhibition Of The Expression Of HIF-1α And Angiogenic Factors With Specific Si RNA Targeting HIF-1α In HCC Cell Under Hypoxia

Angiogenesis plays a key role in the process of tumor growth by providing abundant oxygen and nutrients to neoplasm and making a channel for the tumor invasion and metastasis. Pro-angiogenic factors released from tumor cells can promote the formation of new blood vessels by functioning on host endothelial cells. Vascular endothelial growth factor (VEGF) and its kinase insert domain containing receptor KDR take part in the process of angiogenesis. The maturity and stabilization of neovascular are dependent on another subfamily of tyrosine kinasereceptor Tie2 and its ligand angiopoietins.Hypoxia, a condition of oxygen deprivation, is a common feature of many forms of solid tumors , It emerges when the stromal vascular system fails to deliver a sufficient amount of oxygen to the growing tumor . As a result, many tumors undergo adaptive genetic and protein changes that allow them to adapt hypoxia microenviroment. Such adaptation also makes the change of tumor's biologic features and expression of hypoxia inducible factor-1 (HIF-1), which has been shown to orchestrate a large number of molecular events required for the adaptation of tumor cells to hypoxia VEGF is one of HIF-1a target gene .Hepatocellular carcinoma (HCC) characterized by rapid growth, early metastasis and high mortality is an intensive vascular-dependent marlignant tumor. Angiogenesis is an initial step for these malignant features, and lots of pro- or anti-angiogenic factors and receptors take part in this process. It is suggested that targeting antiangiogenic signaling pathways may be a potent treatment for the prohibition of tumor invasion and metastasis.but many signaling pathway's mechanism is not elucidated. RNAi is a powerful tool to inhibit the target gene expression by post-transcriptional gene silencing.