| Summary: | 碩士 === 國防醫學院 === 微生物及免疫學研究所 === 104 === Background: Hypoxia is an important trigger for human cancer, including metastases and angiogenesis. Previous studies found cancer cells under hypoxic environment initiates hypoxia-induced factor 1α (HIF-1α) signaling pathways to promote tumor growth and angiogenesis. Many clinical studies have shown that inflammation is one of the events in promoting tumorigenesis. Nuclear factor kappa B (NF-κB) pathway plays a pivotal role in cancer inflammation. In 1863, the father of cellular pathology of Rudolf Virchow first proposed an association between chronic inflammation and tumorigenesis, as he observed that tumor cells often peripheral leukocyte infiltration. Among a variety of inflammatory cells, macrophage is the key player of the chronic inflammatory response in view of a great number of bioactive products released from macrophages. These mediators form part of the body's powerful defense against invasion and injury. However, persistent or pathological macrophage activation can result in continued tissue damage. To date, a potential link between hypoxia and cancer inflammation a hypoxic tumor microenvironment for esophageal squamous cancer cell (ESCC) remains poorly defined.
Methods: First, we establish a model for ESCC co-culture with tumor-associated macrophages (TAMs) under hypoxia condition. In order to known what the regulation of HIF-1α in relation to activation of NF-κB in ESCC cell line. We employed a pharmacologic approach using a HIF-1α inhibitor, FM19G11, to examine the effects of HIF-1α transcription by FM19G11 on proliferation, migration, and invasion of ESCC cells. Results：Emplyoing a model of simulated hypoxic tumor microenvironment, we were able to induce hypoxia and inflammation of ESCC cesss. Our results show that under hypoxia associated with M2 macrophages in the tumor microenvironment may promote cell proliferation, migration and invasion, Hypoxia caused activation of HIF-1α / VEGF pathway, resulting in cancer angiogenesis. M2 macrophages promoted the activation of NF-κB. Further, HIF-1α inhibitor, FM19G11, effectively inhibited HIF / NF-κB pathway and reduced the proliferation and mobility of ESCC cells.
Conclusions ：Our results indicate that the tumor microenvironment formed by the M2 macrophages and induce hypoxia may promote tumor development, such as angiogenesis, invasion and metastasis of tumor adjustment, while the activation of the inflammatory response, The above phenomenon can be effectively utilized HIF-1α inhibitors FM19G11 decreased.
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