Study On Reversing Hypoxia-Induced Chemo-and Radio-resistances By Targeting On Hypoxia Inducible Factor-1α In Lung Cancer Cells

INTRODUCTIONHypoxia, a reduction in the normal level of tissue oxygen tension, occurs in several pathophysiological processes including tumorigenesis. It is partly the results of unlimited growth of tumor cells, insufficient blood supply and angiodysplasia, but the mechanism remains unclear. Although hypoxia induces a situation unfavorable for cell growth, cancer cells may undergo a series of genetic and metabolic changes that allow them to survive and even proliferate. For example, hypoxia increases angiogenesis, enhances energy metabolism, increases erythrocytopoiesis, regulates cell cycle and inhibits apoptosis (Severe hypoxia induce apoptosis). Tumor hypoxia had been shown to be an independent prognostic indicator of poorly clinical outcome for cancer patients and to correlate with increase of tumor invasion and metastasis, as well as to resist to certain chemotherapeutic agents.In the process of tumor cells adapting to hypoxia, more than 100 genes involved. Most of them contain a hypoxia response element (HRE) in the flank regions. Hypoxia inducible factor (HIF) regulates the transcription of them through binding to HRE. Therefore, we can block the adaptation response of tumor cells to hypoxia by disruption of HIF-1 pathway, as a consequence, to reverse the resistance to therapy.Hypoxia-inducible transcription factor (HIF-1) is a major transcription...