重组人血管内皮抑制素联合FOLFIRI方案对小鼠结肠癌抑制作用的研究

Recombinant human endostatin combined with FOLFIRI inhibits colorectal cancer in mice

目的探讨重组人血管内皮抑制素(endostar,商品名恩度)联合伊立替康+亚叶酸钙+5-FU(FOLFIRI)方案抑制小鼠结肠癌生长及肝转移的作用。方法 40只BALB/c小鼠通过脾脏注射肿瘤细胞法建立结肠癌肝转移模型,按随机数字表法分为:①模型对照组;②恩度治疗组;③FOLFIRI组;④恩度联合FOLFIRI组(n=10)。模型建立的第2天开始按照制定的给药方案腹腔注射给药。第21天观察、比较各组小鼠脾脏种植瘤的体积,检测种植瘤的凋亡指数(apoptotic index,AI)、肿瘤微血管密度(microvessel dencity,MVD)和血清中的VEGF浓度以及肝脏转移瘤的情况。结果与模型对照组相比,恩度治疗组、FOLFIRI组、恩度联合FOLFIRI组脾脏种植瘤的体积、微血管密度、VEGF含量、肝脏转移瘤数目均减小(P<0.05),脾脏种植瘤的AI升高(P<0.05)。与恩度联合FOLFIRI组相比,恩度治疗组、FOLFIRI组脾脏种植瘤的体积、微血管密度、VEGF含量、肝脏转移瘤数目增大(P<0.05),脾脏种植瘤的AI减小(P<0.05)。结论恩度联合FOLFIRI可以促进结肠癌的凋亡,抑制结肠癌的生长及肝转移。

Objective To investigate the inhibitory effect of recombinant human endostatin combined with FOLFIRI（irinotecan,calcium folinate and 5-FU） on the growth and liver metastasis of colon cancer in mice.Methods A total of 40 BALB/c mice were induced to colon cancer model with liver metastasis by injecting colorectal cancer cells（1×106） into the subcapsule of spleen.They were divided randomly into 4groups（n=10）,model group（normal saline,for 21 d）,endostatin treatment group（2 mg/kg,once per day for 14 d）,FOLFIRI treatment group（irinotecan 40 mg/kg,once per day; calcium folinate 50 mg/kg,once per day or 2 days; 5-FU 300 mg/kg,once per day or 2 days）,and combination treatment group（with endostatin combined with FOLFIRI）.The corresponding agents or normal saline were injected intra-peritoneally to the mice of above groups since the day after model establishment.After 21 days＇ treatment,the volume of tumor masses,apoptotic index（AI） and microvessel density（MVD） were observed with TUNEL and immunohistochemical assay.The serum level of VEGF was detected by enzyme linked immunosorbent assay（ELISA）.The liver metastasis was also observed.Results Compared with model group,the size of spleen implanted tumor,MVD,serum level of VEGF and number of liver metastasis were all reduced obviously in the endostatin,FOLFIRI and combination treatment groups（P0.05）,and AI was significantly increased（P0.05）.The combination treatment group had significantly smaller tumor size,lower MVD and serum level of VEGF,reduced number of liver metastasis,and higher AI when compared with the single treatment groups（P0.05）.Conclusion Recombinant human endostatin combined with FOLFIRI can inhibit the growth and liver metastasis in colon cancer.