复方氟尿嘧啶多相脂质体对S180荷瘤小鼠肿瘤生长抑制及其不良反应

Antitumor effects and toxicity of 5-fluorouracil polyphase liposome in sarcoma 180 tumor-bearing mice

目的:比较复方氟尿嘧啶多相脂质体(Co-5-FU)和氟尿嘧啶(5-FU)对小鼠肉瘤细胞系S180荷瘤小鼠的抗肿瘤作用及不良反应。方法:将小鼠肉瘤S180细胞悬液接种于小鼠背部皮下或腹腔,建立S180荷瘤小鼠实体瘤和腹水瘤模型。取70只小鼠,分成实验组(Co-5-FU)、阳性对照组(5-FU)和正常对照组,分别腹腔注射40 mg·kg^(-1)、20 mg·kg^(-1)、10 mg·kg^(-1)3种不同浓度的Co-5-FU和5-FU,正常对照组腹腔注射生理盐水。比较Co-5-FU和5-FU对实体瘤小鼠的肿瘤抑制率,腹水瘤小鼠的生命延长率,同时通过血生化和病理等检测观察2种药物对各脏器的不良反应。结果:与正常对照组比较,40 mg·kg^(-1)、20 mg·kg^(-1)、10 mg·kg^(-1) Co-5-FU对S180腹水瘤小鼠的生命延长率分别是52．7％,41．4％和31．9％(P＜0．05),对S180实体瘤小鼠的肿瘤抑制率分别是48．8％和39．2％和32．0％(P＜0．01);同等剂量Co-5-FU比5- FU引起的骨髓抑制轻(P＜0．05);40 mg·kg^(-1)5-FU可引起肝脏ALT、AST、GGP升高(P＜0．05)。结论: Co-5-FU比同等剂量的5-FU具有更强的抗肿瘤作用,对心脏、肾脏、肝脏、骨髓的不良反应明显小于5- FU。

AIM： To compare the antitumor effects and toxicity of 5-fluorouracil polyphase liposome （Co-5-FU） with 5-fluorouracil （5-FU） in sarcoma 180 tumor-bearing mice. METHODS ： The models of solid tumors were produced by intradermal injection of sarcoma 180 cells on the back skin and ascite tumors were established by intraperitoneal injection of sarcoma 180 cells in mice. Seventy mice were randomized into 7 groups and were treated with intraperitoneal injection of Co-5-FU （40 mg·kg^-1, 20mg·kg^-1, 10 mg·kg^-1） or 5-FU （40 mg-kg-1, 20mg·kg^-1, 10 mg·kg^-1）, respectively. Mice in normal control group were treated with normal saline. The inhibitory rate of solid tumors and the survival ratio of ascite tumors were calculated. The toxicity of Co-5-FU and 5-FU were evaluated by biochemical and pathological examination. RESULTS： The inhibitor rates was 48.8 %, 39.2 % and 32.0 % （P 〈 0.01 ） and the survival ratios was 52.7 %, 41.4 % and 31.9 % （P 〈 0.05） in Co-5-FU group of 40mg·kg^-1, 20mg·kg^-1 and 10 mg·kg^-1, respectively. Myelosuppression induced by Co-5-FU were less severe than that induced by 5-FU at the same dose （P 〈 0.05）. AST, ALT, ALP and GGT of hepatic enzymes increased in 5-FU group of 40 mg·kg^-1 （p 〈 0.05）. CONCLUSION： The antitumor effects of Co-5-FU are better than 5-FU and the toxicity of Co-5-FU to heart, liver, kidney and medulla is lower than that of 5-FU at the same dose.