重组人血管内皮抑制素联合顺铂对Lewis肺癌小鼠肿瘤微环境的影响

Effect of recombinant human endostatin combined with DDP on tumor microenvironment in Lewis lung carcinoma mice

目的观察重组人血管内皮抑制素(恩度)联合顺铂治疗Lewis肺癌C57BL/6小鼠皮下移植瘤模型的治疗效应,进一步探讨恩度改善肿瘤微环境进而提高治疗效果的作用机制。方法将Lewis肺癌荷瘤鼠分为4组,分别为生理盐水组(A组)、恩度组(B组)、顺铂组(C组)及联合组(恩度+顺铂D组),连续给药15 d。给药期间每日观察小鼠一般状态,测量肿瘤长短径,绘制肿瘤体积曲线,开始给药后第21天处死全部小鼠取出肿瘤组织,计算抑瘤率。常规固定,免疫组化检测缺氧诱导因子1α(HIF-1α)、CD105的表达。结果随给药时间延长,以A组小鼠的精神、饮食、活动、毛色等基本状况为标准,以C组最差,D组最好,B组介于A组与D组之间。各组小鼠肿瘤体积均呈增大趋势,以A组增大最明显,A组>B组>C组>D组,抑瘤率差异均有统计学意义(P<0.05),以A组为0,D组最高,B组高于C组。免疫组化结果显示HIF-1α、CD105呈正相关,差异有统计学意义(r=0.52,P<0.05)。结论恩度联合顺铂能有效控制小鼠肿瘤生长,恩度可改善肿瘤微环境,进而增敏顺铂的化疗作用。

Objective To observe the therapeutic effect of recombinant human endostatin combined with DDP to treat C57BL/ 6 mouse hypo - transplantation tumor model,and to further investigate the mechanism of treatment of endostatin improving the tumor microenvironment. Methods Lewis lung cancer mice were divided into 4 groups to receive the intraperitoneal injection of physiological saline （group A）,endostatin （group B）,DDP （group C）,endostatin plus DDP （group D）,Continual treatment was 15 days. The general station of mice during treatment was observed. The major diameter and short diameter of tumor were measure everyday,and described the tumor volume curve. At the 21th day after treatment,the all mice were sacrificed,and their tumor tissue were taken out,calculated the anti - tumor rate,then fixed,detected HIF - 1α and CD105 by immunhistochemisty. Results With the extension of treatment,the spirit,diet,activities,and the colour of group C was the worst, group D was the best,and group B was better than group A. The tumor volume of each group increased gradually,and group A was the most obvi-ous,group B / C / D by turns. The anti - tumor rate was statistical significance （P 〈 0. 05）. Spearman correlated analysis showed that HIF -1αexpression was positive correlated with CD105 （r = 0. 52,P 〈 0. 05）. Conclusion Endostatin combination with DDP can control the tumor growth effectively. Endostatin can make better the tumor microenvironment and further improve the treatment effect of DDP.