靶向表皮生长因子受体和血管内皮生长因子受体-2治疗多形性胶质母细胞瘤

目的 观察靶向表皮生长因子受体(EGFR)的单克隆抗体C225和靶向血管内皮生长因子受体-2(VEGFR-2)的单克隆抗体DC101单独或联合应用后对人脑多形性胶质母细胞瘤(GBM)裸小鼠脑内移植瘤的疗效.方法 将40只荷瘤鼠随机分为磷酸盐缓冲液(PBS,0.1 ml/20 g·次)、C225(50 mg/kg·次)、DC101(40 mg/kg·次)及C225+DC1O1(50+40 ms/ks·次)等4组,10只/每组,2d1次腹腔用药或PBS,共4次.治疗后观察移植瘤微血管密度(MVD)、体积、形态、增殖和凋亡变化.结果 与对照组比较,DCl01组移植瘤MVD减少了64.O%.体积下降了59.7%,增殖指数下降了53.2%,凋亡指数增加了66.7%(P＜0.05),但肿瘤侵袭性增强;C225组肿瘤侵袭性降低,但对移植瘤MVD、体积、增殖和凋亡无影响(P＞0.05);C225+DC101组移植瘤MVD减少了68.0%,体积下降了62.9%,增殖指数下降了56.4%,凋亡指数增加了75.0%(P＜0.05),肿瘤侵袭性明显下降.结论 DC101抑制血管生成同时增加了肿瘤的侵袭性,而C225能降低肿瘤侵袭性.联合用药不仅抑制GBM移植瘤生长还降低肿瘤侵袭能力.

The inhibitive effect of targeting epidermal growth factor receptor and vascular endothelial growth factor receptor-2 on transplanted human glioblastoma multiforme in nude mice

Objective To explore the inhibitive effect on transplanted human glioblastoma multiforme in the brain of nude mice after treatment of C225 targeting the epidermal growth factor receptor (EGFR)and DC101 targeting the vascular endothehal cell growth factor receptor(VEGFR2)alone and combined application.Methods Forty mice bearing xenografts were divided into 4 groups randoInly with 10 every group,then 4 groups of mice received i.P.injections of C225(50 mg/ks),DC101(40 mg/kg),C225+DC101 or PBS(0.1 ml/20g)respectively 4 times,once every 2 days.On the day 14 post-treatment,mice were sacrificed.Murine brains were removed and fixed in formalin,then tumor appearance and volume were obserred,meanwhile microvessel density,proliferation and apoptosis index were also detected bv immunohistochemical or TUNEL methods.Results Compared with the control group.tumor volume was decreased by 59.7%.microvessel density was decreased by 64.0%,KI-67 LI was decreased by 53.2%,and AI was increased by 66.7%in DC101 group(P＜0.05),but tumor invasiveness was increased:C225 could reduce tumor invasiveness,but had no effect on the volume,Ki-67 LI or AI of tumor (P＞0.05):Tumor volume was decreased by 62.9%(P＜0.05),microvessel density was decreased by 68.0%,Ki-67 LI was decreased by 56.4%and AI was increased by 75%in C225+DC101 group(P＜0.05),invasiveness was also decreased significantly.Conclusion DC101 could inhabit the angiogenesis,and simultaneously could increase the tumor invasiveness,while the C225 could reduce tumor invasiveness.Combined of DC101 and C225 could significantly inhibit GBM tumor growth and reduce the capacity of tumor invasion as compared with DC101 or C255 used alone.