奥沙利铂联合5-氟尿嘧啶治疗癌性腹腔积液的实验研究

The effects of combination treatment of oxaliplatin and 5-fluorouracil on carcinomatous ascites in mice

目的研究奥沙利铂(L-OHP)联合5-氟尿嘧啶(5-FU)治疗小鼠癌性腹腔积液的作用。方法建立小鼠癌性腹腔积液模型,30只成模小鼠随机分为Ⅰ组、Ⅱ组、Ⅲ组,每组10只。接种后第14天起开始腹腔内用药(0.2 ml/只),Ⅰ组给予L-OHP(6 mg/kg)+5-FU(20 mg/kg),Ⅱ组给予DDP(5 mg/kg)+5-FU(20 mg/kg),Ⅲ组为对照组给予0.9%NaCl。均隔日用药,共7次(2周)。测量用药前和用药后2周小鼠的腹围,用药后2周取腹水计量,观察小鼠生存期。采用流式细胞仪法观察L-OHP对肝癌细胞内活性氧的影响。结果用药后2周,Ⅲ、Ⅱ、Ⅰ3组小鼠腹围和腹水量依次减少(P均<0.01),存活率依次升高(P<0.01);随L-OHP剂量的上升(0、16、32、64、128、256μmol/L),作用于HepG2细胞2 h后,细胞内活性氧分别为(4.3±1.2)%、(22.1±2.1)%、(29.9±2.8)%、(40.6±3.0)%、(54.5±3.7)%、(80.1±5.7)%,呈剂量依赖性递升(P<0.01)。结论 L-OHP联合5-FU能抑制小鼠癌性腹腔积液的形成,提高存活率,其效果优于DDP联合5-FU;L-OHP能诱导肝癌HepG2细胞内活性氧的产生,呈明显的剂量依赖性。

Objective To investigate the effects of combination treatment of oxaliplatin （L-OHP）and 5- fluorouracil（5-FU） on carcinomatous ascites in mice. Methods The hepatocellular carcinoma cell line was cuhured and injected into the abdominal cavity of KM mice to establish the carcinomatous ascites model. Thirty KM mice were randomly divided into three groups：group I , group Ⅱ and group Ⅲ（n = 10 each）. Two weeks after implantation, the treatment by peritoneal injection was performed every other day （0.2 ml/mouse） for two weeks ： L-OHP（6 mg/kg） ± 5-FU （20 mg/kg）in group I, cisplatinum （DDP, 5 mg/kg） ± 5-FU （20 mg/kg） in group Ⅱ and 0.9% NaC1 （ as control） in group Ⅲ were respectively given. The abdomen circumference of mice was measured before medication and two weeks after medication. The volume of ascites was measured 14-day after treatment. The survival time of mice was observed. The effects of L-OHP on reactive oxygen in hepatocellular carcinoma cell lines HepG2 were observed through flow cytometry. Results In 14-day after treatment, the abdomen circumference and volume of ascites in groups 11I, II and I decreased in turn （ all P 〈 0. 01 ） , and survival rate increased in turn （P 〈 0. O1 ）. After 2 hours of L-OHP treatment at different concentrations （0,16,32,64,128 and 256 lxmol/L）, the reactive oxygen in HepG2 cells increased in dose-dependent manner [ （4.3 ± 1.2 ） %, （ 22.1 ± 2.1 ） %, （ 29.9 ± 2. 8 ） %, （40.6 ± 3. 0） %, （54.5 ±3.7）% and （80.1 ±5.7）% ;P〈0. 01]. Conclusions Combination treatment of L-OHP and 5-FU could suppress the formation of carcinomatous ascites and increase the survival rate, and its efficacy is superior to the combination of DDP plus 5-FU. L-OHP could induce the formation of reactive oxygen in HepG2 cells in dose- dependent manner.