抗表皮生长因子受体单链抗体联合放化疗治疗裸鼠移植胰腺癌的研究  

The combination of rAAV-anti EGFR with gemcitabine and radiation in pancreatic cancer

作　　者：王天笑[1] 徐建威[1] 郑连芳 万世奇[3] 张太平[1] 赵玉沛[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院基本外科,100730 [2]核医学科 [3]北京积水潭医院

出　　处：《中华肝胆外科杂志》2013年第4期291-295,共5页Chinese Journal of Hepatobiliary Surgery

基　　金：国家自然科学基金（30972896）

摘　　要：目的针对表皮生长因子受体（EGFR）的腺相关病毒（AAV）介导的靶向治疗作为一种新的治疗方式具有广阔的前景。实验通过对胰腺癌细胞株Asp^l进行抗EGFR抗体的重组腺相关病毒（rAAV-antiEGFR）治疗及联合放疗、吉西他滨（简称化疗）等综合治疗手段，探索rAAV介导抗EGFR单链抗体对胰腺癌治疗的效果。方法分别通过单纯化疗、单纯放疗、rAAV-antiEGFR治疗，rAAV-antiEGFR治疗联合化疗、rAAV—antiEGFR治疗联合放疗、rAAV-antiEGFR治疗联合放化疗干预胰腺癌细胞株Aspc-1及裸鼠移植瘤，检测细胞或移植瘤的凋亡率以及移植瘤生长情况。结果体外实验提示，以上处理方式使肿瘤细胞凋亡率显著高于对照组（P〈0．05），rAAV-antiEGFR治疗联合放化疗细胞凋亡率要高于rAAV-antiEGFR治疗、单纯放疗或单纯化疗（P〈0．05）。体内实验提示，rAAV—antiEGFR治疗后，肿瘤生长明显受到抑制（P〈0．05），且与放疗和化疗均有协同作用；rAAV-antiEGFR治疗后，组织中凋亡相关Caspase-3活性蛋白表达细胞数要显著高于对照组（P〈O．05），rAAV-antiEGFR治疗联合放疗或化疗其凋亡蛋白表达细胞数要多于单纯治疗组（P〈0．05）。结论rAAV—antiEGFR治疗在体内外均有良好的抗胰腺癌效应，其联合放化疗疗效优于单纯放疗或单纯化疗，且该病毒载体与化疗及放疗具有协同作用。Objective EGFR targeted therapy mediated by adeno-associated virus is a promising way to treat pancreatic cancer. This study aimed to assess the feasibility and activity of combining rAAV-anti EGFR, gemcitahine, and radiation in pancreatic cancer cells. Methods Aspc-1 human pancreatic carcinoma cells were divided into several groups, in vitro and in vivo, which were respec- tively exposed to gemcitahine alone, radiation alone, rAAV-anti EGFR alone, the combination of rAAV-anti EGFR with gemcitahine, the combination of rAAV-anti EGFR with radiation, and the combination of all three agents. The pancreatic cancer tumor growth and apoptotic rate were meas- ured. Results The apoptotic rate was higher in cells treated with a single or combination of agents compared to the negative control （P〈0.05）. The combination of rAAV-EGFR, gemcitabine, and ra- diation produced the highest induction of apoptosis compared to a single agent alone （P〈0. 05）. Treatment with rAAV-anti EGFR greatly inhibited growth in the tumor xenografts （P〈0.05）, and a synergistic effect of rAAV-anti EGFR, gemcitabine, and radiation was found. The number of tissue cancer ceils that expressed cleaved caspase-3 after treatment with rAAV-EGFR was more than that of the control group （P〈0.05）. The combined treatment of rAAV-anti EGFR, gemcitabine, and radia- tion induced the highest numbers of ceils expressing cleaved caspase-3 compared to that with a single agent alone （P〈0.05）. Conclusions The rAAV-anti EGFR therapy in combination with chemothera- py and radiation therapy demonstrated a greater efficacy over therapy with a single agent alone. rAAV-anti EGFR increased the efficacy of gemcitabine and radiation in the treatment of pancreatic cancer cells.

关 键 词：胰腺肿瘤 表皮生长因子受体 基因疗法 放射疗法 药物疗法 

分 类 号：R735.9[医药卫生—肿瘤]