UVA辐射联合鸦胆子苦醇诱导人恶性黑色素瘤A375细胞凋亡的研究-生物学专业论文.docxVIP

重庆大学 重庆大学硕士学位论文 英文摘要 PAGE PAGE VI ABSTRACT Background: Melanoma is a highly malignant skin tumor. Though there are extensive studies, it’s still one of the worst skin cancers across the globe. Numerous factors contribute to its resistance to hosts of treatment regimes, such as protection from endoplasmic reticulum (ER) stress, over expression of multidrug resistance proteins, efficient DNA repair mechanisms and some other complex phenotypes. Treatment options for patients with metastatic melanoma have been very limited because of higher malignancy and epidemics. In addition, melanoma is not sensitive to chemotherapy and radiation therapy hence proven resistant type of cancers to almost all treatment types. BRAF mutations have been detected in approximately 65% of cutaneous melanomas. Most treatment regimes of melanoma focus on selective small-molecule inhibitors of V600-mutant BRAF gene (such as vemurafenib and dabrafenib). Lots of single-modality medication and treatment methods are often initially effective, but recurrence due to acquired resistance to single-modality medication treatment less than one year is a frequent clinical problem. Due to strong drug resistance of malignant melanoma, we chosen an important and widespread over-expression resistant, cytoprotective and chemopreventive transcription factors in cancer cells: NF-E2-Related Factor 2 (Nrf2) as the breakthrough point. Brusatol, isolated from Brucea javanica plant, is identified as a unique inhibitor of Nrf2-ARE pathway in certain cancer cells. A little is known about the biological effects of brusatol on melanoma cells (A375), and no any study or report is in knowledge to date about brusatol alone or in combination with UVA therapy to treat melanoma cells/tumors. Objects: To examine the influence of a range of UVA doses (25, 50, 75, 100 kJ/m2) and an optimum concentration (50 nM) of brusatol on proliferation of A375, an