表皮生长因子受体单克隆抗体对胶质瘤U87细胞放疗敏感性的影响

Effects of anti-epidermal growth factor receptor monoclonal antibodies on radiosensitisation of U87MG glioma cells

目的探讨表皮生长因子受体（EGFR）单克隆抗体对胶质瘤放疗敏感性的影响及其机制。方法U87胶质瘤细胞体外培养，建立小鼠的皮下和颅内胶质瘤动物模型，予以尼妥珠单抗或西妥昔单抗或联合两种抗体治疗，同时予以放疗，取各组实验肿瘤标本，计算相对肿瘤体积，比较治疗前后卫星肿瘤频率变化以及细胞增殖，比较各组以上结果的差异。结果尼妥珠单抗和西妥昔单抗可增强体内U87MG肿瘤放疗敏感性，h-R3tRT和C255tRT组的中位RTV分别为2．2及2．8，与对照组中位RTV3．5比较差异有统计学意义。小鼠接受抗体的治疗后，卫星肿瘤数量减少了40％～80％，h-R3tRT组及C255tRT组卫星肿瘤频率分别为（9、1～25）和（4、0～17），与对照组卫星频率（18、3～40）比较差异有统计学意义。联合组尼妥珠单抗加强了放疗引起的增殖抑制为56．5％，而单独抗体组和单独放疗组分别为39．9和19．9％，而西妥昔单抗无论单独使用（7．8％），还是与放疗联用（21．7％），不产生明显的细胞增殖抑制作用。结论EGFR单克隆抗体可增强U87MG细胞的放疗敏感性。

Objective To study the influence of anti-epidermal growth factor receptor monoclonal antibodies on the radiosensitisation of U87MG glioma cells. Methods U87 glioma cells were cultured, and the models of mouse subcutaneous and intracranial gliomas were established. Nimotuzumab and cetuximab, alone and in combination with radiation were given in a human GBM xenografted in NMRI nude mice. Tumor specimens were taken out, and the relevant tumor volume was calculated. The difference in satellite tumors and cell proliferation of each group were compared. Results The RTV in h-R3tRT group and C255tRT group was 2. 2 and 2. 8, which was significantly different from that in control group. In mice receiving antibodies-based therapies a 40% -80% reduction in the number of satellite tumors was detected. The frequence of satellite tumors in h-R3tRT and C255tRT was （9, 1-25） and （4, 0-17） respectively, which was significantly lower than in control group （18, 3-40）. In combination group, antibody alone group and radiotherapy alone group, inhabitation rate of proliferation was 56. 5% , 39. 9% and 19. 9% re- spectively. Both cetuximab alone （7.8%）, or combined with radiation （21.7%）, had no significant effect on inhibition of cell proliferation. Conclusion Epidermal growth factor receptor monoclonal antibody could enhance the radiosensitivity of U87MG.