IL-6通过AKT信号通路促进胃癌细胞的侵袭和增殖

发布时间：2018-01-05 01:07

本文关键词：IL-6通过AKT信号通路促进胃癌细胞的侵袭和增殖　出处：《兰州大学》2016年硕士论文　论文类型：学位论文

更多相关文章： IL-6 胃癌 Akt 侵袭增殖 MMP-9 c-Myc

【摘要】：目的:全世界范围,多发恶性肿瘤中胃癌的发病率排第六,死亡率却排第四。尽管近年来胃癌的发病率在一些地区有所下降,但由于大多数胃癌患者一经诊断就处于进展期,预后差,使我们面临着巨大的挑战。作为细胞因子家族里重要成员,白介素-6(Interleukin-6,IL-6)已经被证明在肿瘤进展过程里扮演着重要角色。有报道显示,在胃癌患者中,血清IL-6水平的升高与肿瘤的分期及不良预后显著相关。但是,人们对IL-6影响胃癌细胞具体机制的了解仍不够确切。在这里,我们试图研究IL-6对胃癌细胞侵袭及增殖的影响,进而深入探索它潜在分子学机制。方法:使用不同浓度的IL-6(0、20、50和100 ng/mL)处理胃癌MKN-45细胞,将IL-6浓度为0 ng/mL作为对照组。分别使用CCK-8实验及Transwell实验检测IL-6对MKN-45细胞增殖及侵袭的影响;使用Western blot方法检测不同浓度IL-6对胃癌MKN-45细胞苏氨酸/丝氨酸蛋白激酶(Serine/threonine Kinase,Akt),磷酸化Akt(p-Akt),金属基质蛋白酶-9(Matrix metalloproteinases,MMP-9)及c-Myc表达水平的影响。使用Akt信号通路抑制剂(SH-5)使Akt信号通路阻断,进一步明确IL-6促进胃癌细胞增殖及侵袭的过程中是否有Akt信号通路参与,同时确定MMP-9及c-Myc是否为Akt信号通路的下游蛋白。结果:CCK-8增值实验和Transwell实验结果表明相比于空白对照组,各实验组结果提示胃癌MKN-45细胞增殖和侵袭能力显著增加,且具有统计学意义(P0.05)。Western blot显示IL-6上调了p-Akt、MMP-9及c-Myc在胃癌MKN-45细胞中的蛋白表达水平。此外,Akt信号通路特异性抑制剂(SH-5)明显抑制了由IL-6诱导的胃癌MKN-45细胞的侵袭和增殖,同时MMP-9及c-Myc在胃癌细胞中的蛋白表达水平下降,这些结果表明IL-6影响胃癌细胞侵袭及增殖过程里有Akt信号通路的参与。结论:IL-6可能经由Akt信号通路增加MMP-9和(或)c-Myc在胃癌细胞内的蛋白表达量,从而促进胃癌细胞的侵袭和增殖。
[Abstract]:Objective: worldwide, the incidence of gastric cancer in multiple malignant tumors ranked 6th, but the mortality rate was 4th. Although the incidence of gastric cancer has decreased in some areas in recent years. However, the majority of gastric cancer patients are in advanced stage once diagnosed, and the prognosis is poor, which makes us face a great challenge. As an important member of cytokine family. Interleukin-6 (IL-6) has been shown to play an important role in tumor progression. It has been reported in patients with gastric cancer. The elevation of serum IL-6 level is significantly correlated with tumor staging and poor prognosis. However, the specific mechanism of IL-6 affecting gastric cancer cells is still not well understood. We try to study the effect of IL-6 on the invasion and proliferation of gastric cancer cells and explore its potential molecular mechanism. Gastric cancer MKN-45 cells were treated with 50 and 100 ng / mL. The effects of IL-6 on the proliferation and invasion of MKN-45 cells were detected by CCK-8 assay and Transwell assay, respectively, when the concentration of IL-6 was 0 ng/mL as control group. Detection of threonine / serine protein kinase (THR) in gastric cancer MKN-45 cells with different concentrations of IL-6 by Western blot. Serine/threonine Kinase. Aktn, phosphorylated Aktnab-Aktnchus, metalloproteinase-9 matrix metalloproteinases. The effect of MMP-9) and c-Myc expression. Akt signaling pathway was blocked by Akt signal pathway inhibitor (SH-5). To further determine whether IL-6 promotes the proliferation and invasion of gastric cancer cells in the process of Akt signal pathway involved. At the same time, it was determined whether MMP-9 and c-Myc were downstream proteins of Akt signaling pathway. Results compared with the blank control group, MMP-9 and c-Myc were found to be the downstream proteins in the Akt signaling pathway. The results of each experimental group indicated that the proliferation and invasion of gastric cancer MKN-45 cells were significantly increased. The results showed that IL-6 upregulated p-Akt by P0.05. Western blot. Protein expression of MMP-9 and c-Myc in MKN-45 cells of gastric cancer. SH-5, a specific inhibitor of Akt signaling pathway, significantly inhibited the invasion and proliferation of gastric cancer MKN-45 cells induced by IL-6. At the same time, the expression of MMP-9 and c-Myc in gastric cancer cells decreased. These results suggest that IL-6 affects the invasion and proliferation of gastric cancer cells with the involvement of Akt signaling pathway. Expression of c-Myc protein in gastric cancer cells. Thus promoting the invasion and proliferation 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】：2016
【分类号】：R735.2

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