一次性CO_2气腹环境下氟尿嘧啶对大鼠肿瘤细胞生长及转移的影响

Effects of Fluorouracil Against The Growth and Metastasis of Tumor Cells in Carbon Dioxide Pneumoperitoneum

目的研究腹腔应用氟尿嘧啶(FU)对肿瘤动物模型CO2气腹操作后肿瘤细胞的生长与转移的作用。方法选取雄性清洁级H-22小鼠50只,全部接种S-180细胞悬液,平均分成5组:单纯种植组、气腹组、气腹+生理盐水组、气腹+低浓度(5.0 g/L)FU组和气腹+高浓度(10.0 g/L)FU组。11 d后全部处死,观察肿瘤腹壁种植情况和瘤重(腹水重量差值),并通过免疫组化方法检测增殖细胞核抗原(PCNA)和血管内皮生长因子(VEGF)的表达水平。结果除气腹+低浓度FU组外,其余3组的瘤重均明显高于气腹+高浓度FU组,差异有统计学意义(P<0.05或P<0.01)。气腹+高浓度FU组抑瘤率为64.5%,气腹+低浓度FU组抑瘤率为43.3%。气腹+生理盐水组穿刺孔种植瘤结节直径明显大于气腹+高浓度FU组和气腹+低浓度FU组,差异有统计学意义(P<0.01)。各组小鼠腹水中肿瘤细胞和种植瘤结节中PCNA和VEGF表达的差异均有统计学意义(P<0.05,P<0.01)。结论腹腔内应用高浓度的FU对于S-180细胞气腹动物模型的瘤重、穿刺孔种植瘤结节有抑制作用,其机理可能与下调PCNA和VEGF的表达有关。

Objective To explore the effects of intraperitoneal chemotherapy with fluorouracil （FU） on the growth and metastasis of tumor cells in carbon dioxide （CO2） pneumoperitoneum. Methods Fifty male H-22 mice of clean grade were selected and randomly assigned into 5 groups in each group with 10.. simple implantation group, pneumoperitoneum group, pneumoperitoneum and NS group, pneumoperitoneum and low concentration （5.0 g/L） of FU group and pneumoperitoneum and high concentration （10.0 g/L） of FU group. All mice were executed after 11 days to observe the weight and the implantation of tumor in abdominal wall. Then the expressions of proliferating cell nuclear antigen （PCNA） and vascular endothelial growth factor （VEGF） were detected by immunohistochemistry. Results The tumor weight was significantly higher in pneumoperitoneum and high concentration of FU group compared with other groups except pneumoperitoneum and low concentration of FU group （P〈0.05, P〈0.01 ）. The inhibition rate of tumor was 64.5 % in pneumoperitoneum and high concentration of FU group. The diameter of port-site implantation nodus was significantly bigger in pneumoperitoneum and NS group compared with pneumoperitoneum and low concentration of FU group and pneumoperitoneum and high concentration of FU group （P〈0.01）. The expressions of PCNA and VEGF of aseites and port-site implantation nodus were significantly different in every group, respectively （P〈0. 05, P〈0.01）. Conclusion There is inhibitive effect of intraperitoneal chemotherapy with high concentration of FU on the growth and metastasis of S-180 tumor cells in CO2 pneumoperitoneum, which may be associated with down-regulation of PCNA and VEGF expressions.