吉非替尼联合靶向EGFR DNA疫苗对小鼠Lewis肺癌细胞体内外的抑制作用

Inhibitory effect of gefitinib combined with DNA vaccine targeting EGFR against mouse lung cancer Lewis cells

目的:探讨吉非替尼(gefitinib)联合靶向EGFR DNA疫苗对小鼠Lewis肺癌体内外的抑制作用。方法:用鸡EGFR与兔IgG Fc段异种融合DNA疫苗pVAX1/cEGFR-rFc免疫小鼠制备抗血清,ELISA方法测定抗血清的效价。MTT法检测Lewis细胞的生长情况。建立Lewis肺癌鼠移植瘤模型,随机分为疫苗组、吉非替尼组、吉非替尼+疫苗组和对照组,观察各组小鼠肿瘤体积、重量及生存情况。结果:pVAX1/cEGFR-rFc DNA疫苗免疫小鼠后抗EGFR血清效价为1∶1 000。与抗血清组或吉非替尼组相比,抗血清+吉非替尼组可显著抑制Lewis细胞的生长(P<0.05)。体内实验显示,吉非替尼+疫苗组小鼠移植瘤生长缓慢,荷留小鼠生存率显著提高(P<0.01)。结论:以EGFR为靶点的DNA疫苗和靶向药物吉非替尼之间具有协同性抗肿瘤作用,DNA疫苗主动免疫可以提高吉非替尼的疗效。

Objective： To observe the inhibitory effect of gefitinib combined with DNA vaccine targeting EGFR against implanted Lewis tumors in mice.Methods： Chicken EGFR L2 domain and rabbit IgG Fc domain fusion pVAX1/cEGFR-rFc DNA vaccine was injected into mice and the titer of anti-EGFR in serum was determined by ELISA.The growth of Lewis cells was measured by MTT.Lewis lung cancer mouse models were established and were randomly divided into vaccine,gefitinib,gefitinib＋vaccine,and control groups.The tumor volume and weight and survival of mice were examined in different groups.Results： The titer of anti-EGFR in mice vaccinated with pVAX1/cEGFR-rFc plasmid was 1∶1 000.The proliferation of Lewis cells in anti-EGFR combined with gefitinib was significantly inhibited compared with those in anti-EGFR and gefitinib groups（P〈0.05）.In vivo results showed that the growth of implanted Lewis tumors in vaccine＋gefitinib group was greatly inhibited,and the survival rate of Lewis-bearing mice was significalty increased（P〈0.01）.Conclusion：DNA vaccine targeting EGFR has a synergistic effect with gefitinib in anti-tumor activity,and this DNA vaccine can increase the efficiency of gefitinib.