HMGA1在结直肠癌中的表达及斑螯干预后的作用研究

发布时间：2018-03-04 23:27

本文选题：结直肠癌　切入点：S100A3　出处：《吉林大学》2014年博士论文　论文类型：学位论文

【摘要】：结直肠癌（colorectal cancer, CRC）是比较常见的消化道恶性肿瘤，它的发病率仅次于胃癌和食道癌，高居全球恶性肿瘤的第四位，每年新增患者约100万人，每年因CRC死亡的人数约50万人。近年来，CRC的发病率正在逐渐增加。同时患者的发病年龄也趋于年轻化。研究显示，结直肠癌的好发部位多为直肠和直肠、乙状结直肠的交界处，占60%左右，发病年龄多在60~70岁之间，50岁以下者还不到20%。CRC前期治疗主要是以手术治疗为主，晚期则是以放化疗为主。据报道，CRC的死亡原因主要由于肿瘤的复发和转移。已有研究表明，HMGA1参与了许多和肿瘤相关基因的转录和调控的过程。另有研究发现，HMGA1在癌细胞中的含量极其丰富，说明HMGA1可能改变染色质的结构。目前，HMGA1在CRC中的高表达具体机制尚未明确。因此，探讨HMGA1在CRC中发病机制中的作用对于临床研究具有重要的现实意义。近年研究表明，S100A3作为S100蛋白家族中重要的癌症因子，已被众多学者公认和广泛的研究。然而，是否S100A3在结直肠癌中发挥着同样重要的作用呢？如果S100A3在结直肠癌中发挥作用，那么与HMGA1蛋白的关系如何呢? 据国内文献报道称，斑蝥是昆虫大斑蝥或者小斑蝥的黄黑色干燥体,拥有攻毒蚀疮、具有逐痪散结的独特功效,人类应用斑蝥治疗癌症疾病已有200多年的发展历史。斑蝥可通过抑制癌细胞对氨基酸的摄取，从而抑制蛋白质的合成，同时刺激淋巴细胞、巨噬细胞及多形核细胞产生白介素，从而提高机体免疫力，增加机体抵抗力，加大对肿瘤细胞的杀伤力而达到治疗的目的；斑蝥抗癌机理则是抑制癌细胞DNA以及蛋白质合成，控制癌细胞线粒体的呼吸和酶的活性。斑蝥素在抑制肿瘤的同时，不降低外周血中的白细胞数量，对机体没有显著的免疫抑制作用，这在抗肿瘤药物中是很少见的，因此备受人们关注。近年来，随着抗肿瘤中药优势的凸显，人们对斑蝥素及它的衍生物的研究越来越多，其中对斑蝥素，斑蝥素酸钠及去甲斑蝥素的研究最多，迄今为止，国内外对于结直肠癌的抑制作用尚未明确。那么，，斑蝥是否可以降低结直肠癌中S100A3和HMGA1的表达，进而起到与化疗药相似的治疗效果呢？本实验将对S100A3蛋白和HMGA1蛋白可能的相互关系进行研究；另外，探讨S100A3和HMGA1蛋白在结直肠癌组织发病机制中的作用以及斑蝥干预后对S100A3蛋白和HMGA1蛋白表达的影响，从而揭示S100A3蛋白和HMGA1蛋白在结直肠癌中的中作用以及斑蝥对结直肠癌干预后的影响，为今后防治结直肠癌提供新的依据。
[Abstract]:Colorectal cancer (CRC) is a common malignant tumor of the digestive tract. Its incidence is second only to gastric cancer and esophageal cancer. It ranks among the 4th malignant tumors in the world, with about 1 million new cases each year. The incidence of CRC is increasing in recent years, and the age of onset is getting younger. Studies have shown that colorectal cancer is more likely to occur at the junction of rectum and rectum, and the junction of sigmoid colorectal cancer. Accounting for about 60%, the majority of the onset age between 60 and 70 years of age or less than 50 years of age is less than 20. CRC treatment is mainly surgical treatment. It is reported that the cause of death of CRC is mainly due to the recurrence and metastasis of tumor. It has been shown that HMGA1 is involved in the transcription and regulation of many tumor-related genes. Cancer cells are extremely rich, It is suggested that HMGA1 may change the structure of chromatin. At present, the mechanism of high expression of HMGA1 in CRC is not clear. Exploring the role of HMGA1 in the pathogenesis of CRC has important practical significance for clinical research. Recent studies have shown that S100A3 as an important cancer factor in S100 protein family has been recognized and widely studied by many scholars. Does S100A3 play an equally important role in colorectal cancer? If S100A3 plays a role in colorectal cancer, what is the relationship between S100A3 and HMGA1? According to domestic literature reports, the cantharidis are the yellow and black dry body of the insect cantharidae or small cantharids.It has the unique function of attacking the poisonous ulcer and dissipating the knot gradually. It has been used for more than 200 years to treat cancer diseases. Cantharidaridis can inhibit protein synthesis by inhibiting the uptake of amino acids by cancer cells, while stimulating the production of interleukin in lymphocytes, macrophages and polymorphonuclear cells. In order to improve the body immunity, increase the body resistance, increase the killing power of tumor cells and achieve the purpose of treatment, the anticancer mechanism of cantharidis is to inhibit the synthesis of DNA and protein in cancer cells. Cantharidin not only inhibits the tumor, but also does not reduce the number of white blood cells in the peripheral blood, and has no significant immunosuppressive effect on the body, which is rare in antitumor drugs. In recent years, more and more researches have been done on cantharidin and its derivatives, including cantharidin, sodium cantharidate and norcantharidin. The inhibitory effect of cantharidin on colorectal cancer is not clear. So, can cantharidin reduce the expression of S100A3 and HMGA1 in colorectal cancer, and then play a similar therapeutic effect with chemotherapeutic drugs? The possible relationship between S100A3 protein and HMGA1 protein, the role of S100A3 and HMGA1 protein in the pathogenesis of colorectal cancer and the effect of cantharidin on the expression of S100A3 protein and HMGA1 protein were studied. This study revealed the role of S100A3 and HMGA1 proteins in colorectal cancer and the effect of cantharidin on colorectal cancer after intervention, and provided a new basis for the prevention and treatment of colorectal cancer in the future.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R737.34

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