吉非替尼和fak sirna协同作用对胃癌细胞增殖的影响-synergistic effect of gefitinib and fak sirna on proliferation of gastric cancer cells.docxVIP

吉非替尼和 FAK siRNA 协同作用对胃癌细胞增殖的影响中文摘要目的：了解胃癌组织中 EGFR 和 FAK 的表达水平与胃癌临床病理特征的关 系；研究吉非替尼与 FAK siRNA 联用，同时阻断 EGFR 和 FAK 信号通路对胃癌 细胞增殖的影响。方法：采用免疫组织化学方法检测胃癌组织中 EGFR 和 FAK 的表达水平， 综合分析检测结果与胃癌临床病理特征的关系，并判断二者是否具有相关性；设 计合成 FAK siRNA 并转染胃癌细胞 SGC7901，运用 western blot 方法检验 FAK siRNA 阻断 FAK 合成的效果；MTT 法检验吉非替尼、FAK siRNA 及两者联合作 用对胃癌细胞增殖的影响。结果：?EGFR 及 FAK 在胃癌组织中的阳性表达率 分别为 69.8%、67.0%，而正常胃组织中两者表达均呈阴性。②EGFR 与胃癌浸 润深度、淋巴结转移、远处转移和肿瘤分期有关（P＜0.05），而与性别、年龄、 肿瘤大小、分化程度无关（P＞0.05）；FAK 与分化程度、浸润深度、淋巴结转 移、远处转移和肿瘤分期有关（P＜0.05），而与性别、年龄、肿瘤大小无关（P＞0.05）；EGFR 及 FAK 在胃癌组织中的表达呈正相关（r=0.636，P＜0.05）。③设计合成的 FAK siRNA 使胃癌细胞中 FAK 的合成明显降低（P＜0.05），FAK 蛋白表达量下降 70%。④吉非替尼组和 FAK siRNA 组在应用药物 72 小时后表 现出显著的抑制胃癌细胞增殖的效果（P＜0.05），而联合用药组 48 小时后便表 现出显著的抑制作用，二者具有协同作用（P＜0.05）。结论：?EGFR 和 FAK 在胃癌组织中高表达，与胃癌的浸润、转移有关。② 吉非替尼和 FAK siRNA 合用可显著抑制胃癌细胞的增殖，抑制作用明显优于单 独使用吉非替尼。关键字：胃癌，表皮生长因子受体，粘着斑激酶，吉非替尼，siRNASynergistic effect of Gefitinib and focal adhesion kinase siRNA on proliferation of human gastric cancer cellAbstractObjective To investigate the relationship between espression of EGFR and FAK in human gastric cancer and the synergistic effect of Gefitinib and FAK siRNA on proliferation of human gastric cancer cell.Methods The expression of EGFR and FAK in gastric cancer was tested by immunohistochemical staining and the relationship between EGFR and FAK was analyzed with clinical pathologic characteristics. FAK siRNA was designed and transfected into the gastric cancer cells line,SGC7901. Decreased expression of FAK blocked by siRNA was detected by western blot. Synergistic effect of Gefitinib and FAK siRNA on gastric cancer cell proliferation was measured by MTT method.Results ?Both EGFR and FAK were over expressed (the percentage were 69.8%,67.0%, respectively) in human gastric cancer tissue. ②The level of EGFR expression was associated with the depth of invasion, lymphatic metastasis, distant metastasis and TNM staging of gastric cancer(P0.05), while had no correlationship with gender,age, tumor size,and the degree of differentiation(P0.05).