重组人血管内皮抑素增强EGFR-TKIs对肺癌的抗瘤作用

Antitumor effect of recombinant human vascular endostatin enhancing EGFR-TKIs on lung cancer

目的探讨重组人血管内皮抑素联合表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)耐药细胞系H1975体外及对裸鼠移植瘤的抗瘤作用。方法建立H1975肺癌细胞系裸鼠移植瘤模型24只,并随机分为对照组、单一用药组和联合用药组,每组各8只,建立H1975肺癌细胞系裸鼠移植瘤模型,对照组小鼠不做任何处理,单一用药组注射恩度,联合用药组注射厄洛替尼和恩度,2周后处死实验鼠,并将肿瘤取出进行测量,分析不同用药方法对裸鼠移植瘤的抗瘤作用。结果随着给药时间的延长,对照组小鼠慢慢精神较差,活动量与饮食量减少,卷缩扎堆,毛色灰暗无光泽度。联合用药组小鼠活动情况与饮食情况基本正常,单一用药组小鼠表现介于两组之间;三组小鼠的肿瘤体积与重量比较,差异有统计学意义(P<0.001),对照组最大,其次为单一用药组,最后为联合用药组;小鼠肿瘤组织中MVD计数与VEGF表达比较,三组小鼠血管内皮细胞生长因子(VEGF)表达与微血管密度(MVD)计数比较,差异有统计学意义(P<0.001),联合用药组的数值最小;两组不同治疗方法对小鼠体内H1975细胞和ECV细胞的抑制作用比较,联合用药组的抑制率明显优于单一用药组,差异有统计学意义(P<0.001)。结论应用恩度与厄洛替尼联合作用于肺癌肿瘤,能够减小肿瘤大小,能够抵抗肿瘤,可以应用在EGFR-TKIs耐药患者中,值得临床推广。

Objective To investigate the antitumor effect of the epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKIs)in combination with recombinant human vascular endostatin on xenograft tumor in nude mice in vitro using drug-resistant cell line H1975.Methods Twenty four nude mouse xenograft tumor models of the H1975 lung cancer cell line were established and randomly divided into the control group,the monotherapy group and the combination group,with 8 mice in each group.Mice in the control group were given no treatment.The monotherapy group was injected with endostar,and the combination group was injected with erlotinib and endostar.After 2 weeks,the mice were sacrificed,and the tumors were removed for measurement to analyze the anti-tumor effect of different medication methods on transplanted tumors in nude mice.Results With the prolongation of administration time,the mice in the control group were in poor spirits gradually,with reduced activity and diet,and their hair color was dark without gloss.The activity and diet of mice in the combination group were basically normal,while those in the single group were between the two groups.Statistically significant differences were observed in the tumor volume and weight among the three groups,with the largest in the control group,followed by the monotherapy group,and the smallest in the combination group(P<0.05).The comparison of MVD count and VEGF expression in tumor tissues of mice showed that the vascular endothelial growth factor(VEGF)expression and microvessel density(MVD)count were statistically significantly different among the three groups.The values were the least in the combination group,with statistically significant differences(P<0.001).By comparing the inhibitory effects of different treatment methods on H1975 cells and ECV cells in mice,it was found that the inhibitory rate of the combination group was statistically significantly lower than that of the monotherapy group(P<0.001).Conclusion The combined action of endostar and erlotinib on lung cancer tumors can reduce the tumor size and resist the tumor, which can be applied in patients with drug resistance to EGFR-TKIs and is worthy of clinical promotion.