吴茱萸碱联合放疗对胃癌BGC823细胞移植瘤模型抗肿瘤作用的影响
发布时间：2018-08-11 10:12
【摘要】：胃癌(gastric cancer)是全球范围内最常见的恶性肿瘤之一,在所有肿瘤中致死率占第二位,每年新发病例可达到98.9万,发展中国家中占有70%的新发病例。如果肿瘤可以完全切除,外科手术将是最有效的治疗方法,并且将会获得很好的预后。然而由于胃癌患者在早期不易发现,2/3的患者就诊时多数已经是晚期,单纯的手术治疗往往达不到理想的效果,并且外科手术对远处转移的病例效果也不理想。而放疗在提高手术切除率,局部控制和长期生存率等方面有明显的疗效。然而由于放疗技术的限制,单独放疗会对周围正常组织产生破坏并导致系列的不良反应。并且大多数肿瘤对辐射并不敏感,很大程度上也影响了放疗的效果。因此,人们希望寻找一种药物联合放疗来克服这些问题,从而治疗癌症。吴茱萸碱(evodiamin, EVO)是吴茱萸干燥以后的近成熟果实里的重要的活性成分,具有促儿茶酚胺分泌、抗肿瘤、止痛、舒张血管等多种药理作用。作为天然植物,其具有毒副作用小的优势。本研究的目的旨在研究吴茱萸碱联合放疗对胃癌BGC823细胞移植瘤模型的抑制作用。方法：建立BALB/c裸小鼠胃癌BGC823细胞皮下移植瘤动物模型,分为空白对照组(control)、EVO组(E)、放疗组(R)、联合治疗组(E+R),治疗结束后观察吴茱萸碱联合放疗对小鼠体内肿瘤生长的影响,根据肿瘤体积绘制肿瘤生长曲线。抑瘤率、HE染色、透射电镜及免疫组化(Bcl-2、Bax、p-Akt、Her-2)等指标检测并进行疗效评价。结果：联合治疗组的肿瘤体积及瘤重得到明显的抑制,抑瘤率达到48.8%,明显高于其他各组(P0.05)。HE切片观察联合组大量的BGC-823细胞坏死,肿瘤细胞萎缩,核分裂像明显减少。透射电镜结果显示联合治疗明显提高细胞凋亡大量细胞出现染色质凝集、核深染、破碎、细胞结构消失等现象。免疫组化结果半定量分析发现联合组Her-2、Akt、Bcl-2表达下调,Bax上调。结论：EVO联合放疗明显抑制胃癌BGC823细胞裸鼠移植瘤的生长,其机制可能为降低Her-2表达,抑制PI3K/Akt通路调节下游分子Bcl-2/Bax,从而促进细胞的凋亡。
[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.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.2
本文编号：2176691
[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.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.2
【共引文献】
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2 吴波;高丹;潘超美;张寿文;;不同方法提取吴茱萸叶片基因组DNA和RNA的比较[J];安徽农业大学学报;2012年01期
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2 卢阿娜;吴茱萸碱防治痛经寒凝血瘀证的药理机制[D];北京中医药大学;2010年
3 李晓玲;吴茱萸碱对人涎腺腺样囊性癌ACC-M细胞侵袭的影响[D];河北医科大学;2010年
4 杨杰;吴茱萸碱抑制HepG2细胞STAT3信号通路研究[D];南京林业大学;2012年
5 田秀丽;吴茱萸碱对SPC-A1细胞微管蛋白表达的影响及机制研究[D];吉林大学;2013年
6 曹志;吴茱萸碱对人胶质瘤U251细胞增殖及凋亡影响的研究[D];苏州大学;2014年
7 贾晓芳;MAPK信号通路在铝致SH-SY5Y细胞死亡过程中的作用[D];山西医科大学;2014年
8 崔娟;吴茱萸碱联合CDK1抑制剂对鼠结肠癌的协同杀伤作用[D];广州中医药大学;2011年
9 魏丽娟;吴茱萸碱对人高转移卵巢癌细胞HO-8910PM的影响[D];浙江大学;2015年
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