CAJ | 학술논문

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Aspc-1进行抗EGFR抗体的重组腺相关病毒(rAAV-anti EGFR)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-anti EGFR治疗,rAAV-anti EGFR治疗联合化疗、rAAV-anti EGFR治疗联合放疗、rAAV-anti EGFR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-anti EGFR治疗联合放化疗细胞凋亡率要高于rAAV-anti EGFR治疗、单纯放疗或单纯化疗(P＜0.05).体内实验提示,rAAV-anti EGFR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-anti EGFR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＜0.05),rAAV-anti EGFR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-anti EGFR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.
목적 침대표피생장인자수체(EGFR)적선상관병독(AAV)개도적파향치료작위일충신적치료방식구유엄활적전경.실험통과대이선암세포주Aspc-1진행항EGFR항체적중조선상관병독(rAAV-anti EGFR)치료급연합방료、길서타빈(간칭화료)등종합치료수단,탐색rAAV개도항EGFR단련항체대이선암치료적효과.방법 분별통과단순화료、단순방료、rAAV-anti EGFR치료,rAAV-anti EGFR치료연합화료、rAAV-anti EGFR치료연합방료、rAAV-anti EGFR치료연합방화료간예이선암세포주Aspc-1급라서이식류,검측세포혹이식류적조망솔이급이식류생장정황.결과 체외실험제시,이상처리방식사종류세포조망솔현저고우대조조(P＜0.05),rAAV-anti EGFR치료연합방화료세포조망솔요고우rAAV-anti EGFR치료、단순방료혹단순화료(P＜0.05).체내실험제시,rAAV-anti EGFR치료후,종류생장명현수도억제(P＜0.05),차여방료화화료균유협동작용;rAAV-anti EGFR치료후,조직중조망상관Caspase-3활성단백표체세포수요현저고우대조조(P＜0.05),rAAV-anti EGFR치료연합방료혹화료기조망단백표체세포수요다우단순치료조(P＜0.05).결론 rAAV-anti EGFR치료재체내외균유량호적항이선암효응,기연합방화료료효우우단순방료혹단순화료,차해병독재체여화료급방료구유협동작용.
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,gemcitabine,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 respectively exposed to gemcitabine alone,radiation alone,rAAV-anti EGFR alone,the combination of rAAV-anti EGFR with gemcitabine,the combination of rAAV-anti EGFR with radiation,and the combination of all three agents.The pancreatic cancer tumor growth and apoptotic rate were measured.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 radiation 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 cells 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 radiation induced the highest numbers of cells expressing cleaved caspase-3 compared to that with a single agent alone (P＜0.05).Conclusions The rAAV-anti EGFR therapy in combination with chemotherapy 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.