中文摘要：

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。

英文摘要：

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.