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[目的]观察不同剂量贝伐单抗与伊立替康联合对人结肠癌裸鼠皮下移植瘤生长及肿瘤血管生成的影响。[方法]接种人结肠癌DLD-1细胞的裸鼠21只,随机分为4组:无菌生理盐水对照组(A组),5mg/kg贝伐单抗联合伊立替康化疗组(B组),10mg/kg贝伐单抗联合伊立替康化疗组(C组)和单纯伊立替康化疗组(D组)(A、B、C组每组各5只,D组6只,各组伊立替康剂量均为66.7mg/kg)。于d1,5,9(q4d×3)分别给药,治疗第10d处死裸鼠,观察肿瘤生长情况,计算抑瘤率,免疫组化法检测肿瘤组织微血管密度(MVD),评价肿瘤坏死情况。[结果]A、B、C、D组肿瘤体积分别为:646.24±397.33mm3、240.11±147.44mm3、346.21±298.59mm3、399.11±254.09mm3。B、C两组比较,肿瘤体积差异未达统计学意义(P=0.208)。与A组比较,B、C、D组抑瘤率分别为62.85%、47.91%、39.59%。A、B、C、D各组微血管密度(microvesseldensity,MVD)分别为7.000±0.71、4.940±0.58、5.080±1.25、5.557±2.04,经Dunnett检验,与A组比,B、C组肿瘤MVD均有显著性差异(P值分别为0.028、0.039),而D组与A组,及B组与C组在MVD表达上差异未达到统计学意义(P值分别为0.086、0.083)。移植瘤组织HE染色后发现各组肿瘤组织内均有不同程度的坏死。其中,对照组多以轻中度坏死为主,用药后坏死面积均增加,各组坏死分级经秩和检验,χ2=4.73,P=0.193。两两间比较,P值均大于0.05,各治疗组间的坏死差异并不明显。治疗组肿瘤细胞的凋亡较明显。[结论]不同剂量贝伐单抗联合伊立替康对荷DLD-1裸鼠移植瘤有抑制作用,联合用药有显著协同作用,推测其作用机制可能与抑制肿瘤微血管形成、诱导细胞凋亡和死亡增加有关。5mg/kg及10mg/kg贝伐单抗对移植瘤体积及MVD上的作用差异不显著。
[Objective] To observe the effect of different doses of bevacizumab combined with irinotecan on the growth of human colon carcinoma xenografts in nude mice and tumor angiogenesis. [Method] Twenty-one nude mice inoculated with human colon cancer DLD-1 cells were randomly divided into 4 groups: sterile saline control group (group A), 5mg / kg bevacizumab combined with irinotecan chemotherapy group (group B ), 10mg / kg bevacizumab combined with irinotecan chemotherapy (group C) and irinotecan chemotherapy group (group D) (5 in each group, 6 in group D, 6 in each group Irinotecan dose was 66.7mg / kg). The mice were killed on the 10th day after treatment, the growth of the tumor was observed, the tumor inhibition rate was calculated, the microvessel density (MVD) of the tumor tissue was detected by immunohistochemistry and the tumor necrosis was evaluated. [Results] The tumor volumes in groups A, B, C and D were 646.24 ± 397.33mm3, 240.11 ± 147.44mm3, 346.21 ± 298.59mm3, 391.11 ± 254.09mm3, respectively. There was no significant difference in tumor volume between groups B and C (P = 0.208). Compared with group A, the inhibition rates of group B, C and D were 62.85%, 47.91% and 39.59% respectively. The microvessel density (MVD) in groups A, B, C and D was 7.000 ± 0.71, 4.940 ± 0.58, 5.080 ± 1.25 and 5.557 ± 2.04, respectively. Compared with group A, the MVD of group B and group C (P = 0.028, 0.039, respectively). However, there was no significant difference in MVD between group D and group A, group B and group C (P = 0.086 and 0.083, respectively). Transplanted tumor tissue HE staining showed that each group of tumor tissue have varying degrees of necrosis. Among them, the control group mostly mild to moderate necrosis, necrosis area increased after treatment, necrosis grading by rank sum test, χ2 = 4.73, P = 0.193. Twelve between the two, P values were greater than 0.05, necrosis differences between the treatment groups is not obvious. The apoptosis of tumor cells in treatment group was more obvious. [Conclusion] Different dosages of bevacizumab combined with irinotecan can inhibit the xenografts in nude mice bearing DLD-1 and there is significant synergistic effect between them. The mechanism may be related to inhibition of tumor microvessel formation and apoptosis induction and death Increase related. The effects of 5 mg / kg and 10 mg / kg bevacizumab on tumor volume and MVD were not significant.