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[目的]在动物体内评价以磺胺嘧啶(SF)为载体的氟尿嘧啶(5-Fu)靶向药物(SFPEG5-Fu)的抗肿瘤疗效及急性毒性。[方法]40只荷肝癌H22小鼠按体重随机分为4组:0.9%NaCl组、SFPEG5-Fu组、5-Fu组、SFPEG+5-Fu(30∶1,m/m)组,每组10只小鼠。生理盐水组作为阴性对照组,其他3组分别以相应5-Fu剂量为20mg/kg的SFPEG5-Fu、5-Fu、SFPEG+5-Fu(30∶1,m/m)尾静脉给药,每天1次,连续给药5d。给药后7d计算肿瘤抑制率。并观察给药组荷瘤小鼠的生存期。SFPEG5-Fu以最大给药剂量、最大给药体积尾静脉一次给药20只健康昆明小鼠,给药第14d处死小鼠。对小鼠进行尸体解剖检查,取肝、脾、肾、肺、胰腺、心脏、胃、肠、胸骨进行常规病理检查了解SFPEG5-Fu的急性毒性。[结果]与生理盐水组相比,SFPEG5-Fu,5-Fu,SFPEG+5-Fu(30∶1,m/m)3组肿瘤生长明显受到抑制(P<0.01),给药后SFPEG5-Fu组小鼠皮下瘤体积小于其他3组(P<0.01),5-Fu组和SFPEG+5-Fu组间小鼠皮下瘤体积无明显差异(P>0.05)。SFPEG5-Fu组小鼠生存期长于5-Fu组、SFPEG+5-Fu组小鼠生存期(P<0.05)及生理盐水组小鼠生存期(P<0.01)。SFPEG5-Fu的最大耐受量为4g/kg,可以认为LD50>4g/kg。组织学检查发现肝细胞出现广泛的气球样变性的改变,有点状坏死,胸骨造血功能有轻到中度抑制。[结论]SFPEG5-Fu对荷肝癌H22小鼠有明显的抑制肿瘤作用及较低的毒性,并可延长荷瘤小鼠的中位生存期。
[Objective] To evaluate the anti-tumor efficacy and acute toxicity of 5-Fu targeted drug (SFPEG5-Fu) with sulfadiazine (SF) as carrier in animals. [Method] 40 H22-bearing HCC mice were randomly divided into 4 groups according to body weight: 0.9% NaCl group, SFPEG5-Fu group, 5-Fu group and SFPEG + 5-Fu (30:1, m / Groups of 10 mice. Saline group as negative control group, the other three groups were given tail vein of SFPEG5-Fu, 5-Fu and SFPEG + 5-Fu (30:1, m / m) 1 day, continuous administration 5d. Tumor inhibition rate was calculated 7 days after administration. The survival of the tumor-bearing mice was observed. SFPEG5-Fu at the maximum dose, the maximum dose volume of tail vein once administered 20 healthy Kunming mice administered mice administered on the 14th day. The autopsy of the mice was performed and the routine pathological examination of liver, spleen, kidney, lung, pancreas, heart, stomach, intestine and sternum was performed to understand the acute toxicity of SFPEG5-Fu. [Results] The tumor growth of SFPEG5-Fu, 5-Fu and SFPEG + 5-Fu (30:1, m / The tumor volume of Fu group was smaller than that of the other three groups (P <0.01). There was no significant difference in the volume of subcutaneous tumor between 5-Fu group and SFPEG + 5-Fu group (P> 0.05). The survival of mice in SFPEG5-Fu group was longer than that in 5-Fu group, SFPEG + 5-Fu group (P <0.05) and saline group (P <0.01). The maximum tolerated dose of SFPEG5-Fu is 4 g / kg, which can be considered as LD50> 4 g / kg. Histological examination revealed a wide range of balloon-like changes in hepatocytes, a little necrosis, mild to moderate inhibition of sternal hematopoietic function. [Conclusion] SFPEG5-Fu can significantly inhibit the tumor and reduce the toxicity of liver cancer H22 mice and prolong the median survival of tumor-bearing mice.