發(fā)布時間：2018-03-04 23:27

  本文選題：結直腸癌　切入點：S100A3　出處：《吉林大學》2014年博士論文　論文類型：學位論文

【摘要】：結直腸癌（colorectal cancer, CRC）是比較常見的消化道惡性腫瘤，它的發(fā)病率僅次于胃癌和食道癌，高居全球惡性腫瘤的第四位，每年新增患者約100萬人，每年因CRC死亡的人數(shù)約50萬人。近年來，CRC的發(fā)病率正在逐漸增加。同時患者的發(fā)病年齡也趨于年輕化。研究顯示，結直腸癌的好發(fā)部位多為直腸和直腸、乙狀結直腸的交界處，占60%左右，發(fā)病年齡多在60~70歲之間，50歲以下者還不到20%。CRC前期治療主要是以手術治療為主，晚期則是以放化療為主。據報道，CRC的死亡原因主要由于腫瘤的復發(fā)和轉移。已有研究表明，HMGA1參與了許多和腫瘤相關基因的轉錄和調控的過程。另有研究發(fā)現(xiàn)，HMGA1在癌細胞中的含量極其豐富，說明HMGA1可能改變染色質的結構。目前，HMGA1在CRC中的高表達具體機制尚未明確。因此，探討HMGA1在CRC中發(fā)病機制中的作用對于臨床研究具有重要的現(xiàn)實意義。近年研究表明，S100A3作為S100蛋白家族中重要的癌癥因子，已被眾多學者公認和廣泛的研究。然而，是否S100A3在結直腸癌中發(fā)揮著同樣重要的作用呢？如果S100A3在結直腸癌中發(fā)揮作用，那么與HMGA1蛋白的關系如何呢? 據國內文獻報道稱，斑蝥是昆蟲大斑蝥或者小斑蝥的黃黑色干燥體,擁有攻毒蝕瘡、具有逐瘓散結的獨特功效,人類應用斑蝥治療癌癥疾病已有200多年的發(fā)展歷史。斑蝥可通過抑制癌細胞對氨基酸的攝取，從而抑制蛋白質的合成，同時刺激淋巴細胞、巨噬細胞及多形核細胞產生白介素，從而提高機體免疫力，增加機體抵抗力，加大對腫瘤細胞的殺傷力而達到治療的目的；斑蝥抗癌機理則是抑制癌細胞DNA以及蛋白質合成，控制癌細胞線粒體的呼吸和酶的活性。斑蝥素在抑制腫瘤的同時，不降低外周血中的白細胞數(shù)量，對機體沒有顯著的免疫抑制作用，這在抗腫瘤藥物中是很少見的，因此備受人們關注。近年來，隨著抗腫瘤中藥優(yōu)勢的凸顯，人們對斑蝥素及它的衍生物的研究越來越多，其中對斑蝥素，斑蝥素酸鈉及去甲斑蝥素的研究最多，迄今為止，國內外對于結直腸癌的抑制作用尚未明確。那么，，斑蝥是否可以降低結直腸癌中S100A3和HMGA1的表達，進而起到與化療藥相似的治療效果呢？本實驗將對S100A3蛋白和HMGA1蛋白可能的相互關系進行研究；另外，探討S100A3和HMGA1蛋白在結直腸癌組織發(fā)病機制中的作用以及斑蝥干預后對S100A3蛋白和HMGA1蛋白表達的影響，從而揭示S100A3蛋白和HMGA1蛋白在結直腸癌中的中作用以及斑蝥對結直腸癌干預后的影響，為今后防治結直腸癌提供新的依據。
[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.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R737.34

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