發(fā)布時間：2018-08-11 10:12

【摘要】：胃癌(gastric cancer)是全球范圍內(nèi)最常見的惡性腫瘤之一,在所有腫瘤中致死率占第二位,每年新發(fā)病例可達到98.9萬,發(fā)展中國家中占有70%的新發(fā)病例。如果腫瘤可以完全切除,外科手術(shù)將是最有效的治療方法,并且將會獲得很好的預(yù)后。然而由于胃癌患者在早期不易發(fā)現(xiàn),2/3的患者就診時多數(shù)已經(jīng)是晚期,單純的手術(shù)治療往往達不到理想的效果,并且外科手術(shù)對遠處轉(zhuǎn)移的病例效果也不理想。而放療在提高手術(shù)切除率,局部控制和長期生存率等方面有明顯的療效。然而由于放療技術(shù)的限制,單獨放療會對周圍正常組織產(chǎn)生破壞并導(dǎo)致系列的不良反應(yīng)。并且大多數(shù)腫瘤對輻射并不敏感,很大程度上也影響了放療的效果。因此,人們希望尋找一種藥物聯(lián)合放療來克服這些問題,從而治療癌癥。吳茱萸堿(evodiamin, EVO)是吳茱萸干燥以后的近成熟果實里的重要的活性成分,具有促兒茶酚胺分泌、抗腫瘤、止痛、舒張血管等多種藥理作用。作為天然植物,其具有毒副作用小的優(yōu)勢。本研究的目的旨在研究吳茱萸堿聯(lián)合放療對胃癌BGC823細胞移植瘤模型的抑制作用。方法：建立BALB/c裸小鼠胃癌BGC823細胞皮下移植瘤動物模型,分為空白對照組(control)、EVO組(E)、放療組(R)、聯(lián)合治療組(E+R),治療結(jié)束后觀察吳茱萸堿聯(lián)合放療對小鼠體內(nèi)腫瘤生長的影響,根據(jù)腫瘤體積繪制腫瘤生長曲線。抑瘤率、HE染色、透射電鏡及免疫組化(Bcl-2、Bax、p-Akt、Her-2)等指標檢測并進行療效評價。結(jié)果：聯(lián)合治療組的腫瘤體積及瘤重得到明顯的抑制,抑瘤率達到48.8%,明顯高于其他各組(P0.05)。HE切片觀察聯(lián)合組大量的BGC-823細胞壞死,腫瘤細胞萎縮,核分裂像明顯減少。透射電鏡結(jié)果顯示聯(lián)合治療明顯提高細胞凋亡大量細胞出現(xiàn)染色質(zhì)凝集、核深染、破碎、細胞結(jié)構(gòu)消失等現(xiàn)象。免疫組化結(jié)果半定量分析發(fā)現(xiàn)聯(lián)合組Her-2、Akt、Bcl-2表達下調(diào),Bax上調(diào)。結(jié)論：EVO聯(lián)合放療明顯抑制胃癌BGC823細胞裸鼠移植瘤的生長,其機制可能為降低Her-2表達,抑制PI3K/Akt通路調(diào)節(jié)下游分子Bcl-2/Bax,從而促進細胞的凋亡。
[Abstract]:Gastric cancer (gastric cancer) is one of the most common malignant tumors in the world, with the second leading cause of death among all tumors, with 989000 new cases per year and 70% of new cases in developing countries. If the tumor is completely resected, surgery will be the most effective treatment and will have a good prognosis. However, due to the fact that it is not easy to find two thirds of the patients with gastric cancer in the early stage, most of them are at the late stage, the simple surgical treatment is often not satisfactory, and the effect of surgical operation on distant metastasis cases is not ideal. Radiotherapy can improve the resection rate, local control and long-term survival rate. However, due to the limitations of radiotherapy techniques, radiation alone can damage the surrounding normal tissue and lead to a series of adverse reactions. And most tumors are not sensitive to radiation, and to a large extent affect the effect of radiotherapy. Therefore, people hope to find a drug combined with radiotherapy to overcome these problems and thus cure cancer. Rutaecarpine (evodiamin, EVO) is an important active component in the dried fruit of Evodia rutaecarpa. It has many pharmacological effects, such as promoting catecholamine secretion, anti-tumor, analgesic, vasodilating and so on. As a natural plant, it has the advantage of less toxic and side effects. The aim of this study was to study the inhibitory effect of rutaecarpine combined with radiotherapy on BGC823 cell transplantation tumor model of gastric cancer. Methods: the animal model of subcutaneous transplantation of gastric cancer BGC823 cells in BALB/c nude mice was established and divided into control group (control) / Evo group), (E), radiotherapy group (R), combined treatment group) and (E R), group (E R), group) after the end of treatment, the effect of Evodipine combined with radiotherapy on tumor growth in mice was observed. The tumor growth curve was drawn according to the tumor volume. The tumor inhibition rate was detected by HE staining, transmission electron microscopy and immunohistochemical staining (Bcl-2Baxa-p-Akthe Her-2), and the curative effect was evaluated. Results: the tumor volume and tumor weight in the combined treatment group were significantly inhibited, and the tumor inhibition rate was 48.8%, which was significantly higher than that in the other groups (P0.05) .HE sections observed the necrosis of a large number of BGC-823 cells, atrophy of tumor cells and decrease of mitotic image in the combined group. The results of transmission electron microscope showed that the combined therapy could obviously increase the number of apoptotic cells, such as chromatin agglutination, deep staining of nucleus, fragmentation, disappearance of cell structure and so on. Immunohistochemical results showed that the expression of Her-2 and Akttfen Bcl-2 was down-regulated and Bax was up-regulated in the combined group. Conclusion the growth of xenografts in nude mice with gastric cancer BGC823 cells was significantly inhibited by the combination of fraction EVO and radiotherapy. The mechanism may be to reduce the expression of Her-2 and inhibit the regulation of downstream Bcl-2 / Bax-pathway by PI3K/Akt pathway, thus promoting apoptosis of gastric cancer cells.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R735.2

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