【作者】 陈杰；

【导师】 王海涛；

【作者基本信息】 苏州大学 ， 外科学（胃肠外科）， 2017， 硕士

【摘要】 目的研究曲妥珠单抗联合奥沙利铂对HER2阳性胃癌细胞增殖及细胞活性的影响,探讨二者联合的可能性及有效性。方法通过查阅文献及Western Blot检测获得HER2阳性胃癌细胞株NCI-N87,设置空白组、曲妥珠单抗组及联合组,通过克隆形成试验、CCK-8增殖试验观察曲妥珠单抗联合奥沙利铂对NCI-N87细胞增殖的影响;通过设置曲妥珠单抗浓度梯度,观察其对NCI-N87细胞活力的影响,并研究曲妥珠单抗与奥沙利铂联合的效果;构建NCG鼠移植瘤模型,通过监测肿瘤增殖情况,绘制肿瘤生长曲线。数据以均值±标准差(x±SD)表示,应用GraphPad Prism 5.0统计软件分析,以P<0.05为差异有统计学意义。结果曲妥珠单抗联合奥沙利铂组细胞克隆集落数量明显低于曲妥珠单抗组(P<0.01),差异有统计学意义;CCK-8增殖试验显示联合组细胞增殖速率明显低于曲妥珠单抗组(P<0.05),差异具有统计学意义;细胞毒性试验显示随着曲妥珠单抗浓度的增加,细胞存活率随之降低,且曲妥珠单抗联合奥沙利铂对HER2阳性胃癌细胞的毒性作用更强(P<0.05);动物模型结果显示联合组肿瘤生长慢于曲妥珠单抗组,肿瘤体积明显小于曲妥珠单抗组(P<0.01),肿瘤重量明显轻于曲妥珠单抗组(P<0.01),差异具有统计学意义。结论曲妥珠单抗联合奥沙利铂能够抑制HER2阳性胃癌细胞NCI-N87的增殖,降低其细胞活性,加强杀伤效应;二者联用有助于抑制胃癌细胞在体内的生长,为曲妥珠单抗联合化疗药物治疗HER2阳性胃癌提供依据。更多还原

【Abstract】 ObjectiveTo research the combination effect of trastuzumab and oxaliplatin on cell proliferation and viability in HER2-positive gastric cancer and explore the potential possibility and validity of them in clinical application.Methods Through review of literature and western blot,we obtain the HER2-positive gastric cancer cell line NCI-N87 and set three groups(negative control group,trastuzumab group and the combination group).The cell proliferation was determined by clony formation assay and CCK-8 assay.The cell viability was determined bydifferent concentration of trastuzumab and then we combined trastuzumab and oxaliplatin to see whether the effectiveness was better.Further,we established the NCG mouse model for HER2-positive gastric cancer cells and investigated tumorigenicity in vivo through monitoring tumor growth.Data was recorded as mean ± standard deviation,and statistically analyzed with Graphpad Prism 5.0.P < 0.05 was used to indicate a statistically significant difference.ResultsTheclony formation assay showed the clonies number of the combination group was significantly lower than number of trastuzumab group(P<0.01).The cell proliferation assay showed thatthe proliferation rate of the combination groupwas significantly lower than trastuzumab group(P<0.05).The cell viability was gradually decreased with the concentration increasing of trastuzumab,and the cell viability of the combination group wassignificantly lower than trastuzumab group(P<0.05).In mouse model,tumorigenicity in vivo was significantly suppressed in the combination group thantrastuzumab group(P<0.01).ConclusionThe combination of trastuzumab and oxaliplatin could significantly inhibit the cell proliferation and viability of NCI-N87 cells in vitro.Besides,the combination of them could also suppress tumorigenicity in vivo.Our results suggest that combining trastuzumab and oxaliplatinhave practical applications in chemotherapy of gastric cancer.更多还原