發(fā)布時(shí)間：2018-03-24 19:13

  本文選題：褐藻糖膠　切入點(diǎn)：多發(fā)性骨髓瘤　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的多發(fā)性骨髓瘤(multiple myeloma,MM)的發(fā)病率在血液腫瘤中排名第三。盡管化療方案的改善、新藥的應(yīng)用及干細(xì)胞移植技術(shù)的成熟使該疾病治療緩解率大大提高,但相當(dāng)一部分患者在數(shù)年或數(shù)月內(nèi)復(fù)發(fā)。有研究表明微小殘留病灶(minimal residual disease,MRD)引起的復(fù)發(fā)是其難以治愈的原因之一。因此,發(fā)現(xiàn)能夠抑制骨髓瘤細(xì)胞遷移、侵襲能力,減少M(fèi)RD的低毒性藥物,對輔助治療有著重要的作用。本研究探討褐藻糖膠對多發(fā)性骨髓瘤U266細(xì)胞自噬、遷移及侵襲的影響,為研究褐藻糖膠治療多發(fā)性骨髓瘤的臨床應(yīng)用提供理論依據(jù)。方法褐藻糖膠處理細(xì)胞后,透射電子顯微鏡(TEM)觀察細(xì)胞自噬小體,Traswell小室觀察細(xì)胞遷徙及侵襲能力,Western Blot測定LC3-Ⅱ/LC3-Ⅰ,Beclin-1,P62,MMP9,CXCR4,p-AKT/T-AKT,p-mTOR/T-mTOR蛋白表達(dá),ELISA法檢測細(xì)胞培養(yǎng)液中MMP9含量。結(jié)果(1)TEM觀察發(fā)現(xiàn),褐藻糖膠處理組自噬小體增加。(2)褐藻糖膠可降低U266細(xì)胞遷移及侵襲能力,并呈現(xiàn)出劑量依賴性,氯喹可阻斷該抑制作用。(3)Western Blot結(jié)果顯示,LC3-II/LC3-I、Beclin-1及MMP9蛋白表達(dá)隨褐藻糖膠濃度增加而升高,P62、CXCR4、p-AKT/T-AKT及p-mTOR/T-mTOR蛋白表達(dá)與褐藻糖膠濃度增加而降低。(4)ELISA結(jié)果顯示,褐藻糖膠處理組細(xì)胞培養(yǎng)液中MMP9的含量下降。結(jié)論褐藻糖膠可誘導(dǎo)多發(fā)性骨髓瘤U266細(xì)胞自噬,抑制該細(xì)胞的遷移、侵襲能力。
[Abstract]:Objective multiple myeloma (MM) is the third most common disease in blood tumors. Despite the improvement of chemotherapy regimen, the application of new drugs and the maturity of stem cell transplantation technology, the remission rate of the disease has been greatly improved. However, a considerable number of patients recurred within a few years or months. Some studies have shown that the recurrence caused by minimal residual disease is one of the reasons for the difficulty of cure. Therefore, it has been found that it can inhibit the migration and invasion ability of myeloma cells. Reducing the low toxicity of MRD plays an important role in adjuvant therapy. In this study, we investigated the effects of fucoidan on autophagy, migration and invasion of multiple myeloma U266 cells. Methods to study the clinical application of fucoidan in the treatment of multiple myeloma. The transmissive electron microscopy (TEM) was used to observe the migration and invasiveness of the cells in the autophagy chamber. Western Blot was used to detect the expression of CXCR4, p-AKTR, p-mTOR-T-mTOR protein in the cell culture medium. In the treatment group, the autophagy increased. 2) Alginate decreased the migration and invasion ability of U266 cells in a dose-dependent manner. Chloroquine blocked the inhibitory effect. Western Blot results showed that the protein expression of Beclin-1 and MMP9 increased with the increase of the concentration of fucoidin, and the expression of P62CXCR4 p-AKT and p-mTOR/T-mTOR protein decreased with the increase of the concentration of fucoidan. Conclusion Alginate can induce autophagy of multiple myeloma U266 cells and inhibit the migration and invasion of U266 cells.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R733.3

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