5-Fu静脉、腹腔化疗诱导小鼠腹水瘤细胞凋亡研究

Study on Apoptosis Induced by 5-Fu Intravenous or Intraperitoneal Chemotherapy in Mice Following Peritoneal Implantation of H22 Cell

为探讨 5 - Fu静脉和腹腔给药途径诱导小鼠腹水瘤细胞凋亡的规律及其抗肿瘤作用机制 ,将 45只腹腔内接种 H2 2细胞的小鼠随机分成对照、静脉和腹腔内化疗 3组。各组于注药后第 3、 5、 7d分别收集腹水细胞行细胞形态观察、DNA电泳分析和流式细胞仪检测。结果显示 ,化疗组腹水细胞均呈现典型细胞凋亡形态学特征 ,同时可见细胞坏死。细胞凋亡率呈时间依赖性 (P<0 .0 1) ,且腹腔内化疗组细胞凋亡率各时间点均明显高于静脉组 (P<0 .0 1)。提示5 - Fu抗肿瘤作用机制是引起肿瘤细胞死亡和诱导肿瘤细胞凋亡共同作用的结果 ;腹腔内化疗效果明显优于静脉化疗。

The mechanism of apoptosis induced by intravenous or intraperitoneal chemotherapy with 5-fluorouracil (5-Fu) in mice following peritoneal implantation of H22 cells were studied. Forty-five mice inoculated with H22 cell suspension intraperitoneally were randomly divided into three groups: A: control group; B: intravenous chemotherapy group with 5-Fu (20 mg/kg every day) for one week after inoculation; C: intraperitoneal chemotherapy group with the same dose of 5-Fu at the same time. On the 3rd, 5th and 7th day, ascites cells of each group were collected. Apoptosis of cells in the ascites were observed by using cytohistochemistry staining, fluorescence staining and electron microscopy scanning, and also were examined by flow cytometry analysis. In addition, total DNA was isolated from the ascites cells and was subjected to electrophoresis through an agarose gel. It was found that typical characteristics of apoptosis and also cell death was showed after chemotherapy. The ratio of apoptosis was enhanced within test time range in a time dependent pattern (P<0.01), and the ratio was higher in the intraperitoneal chemotherapy group than in the intravenous chemotherapy group at each time point (P<0.01). It was suggested that the mechanism of 5-Fu against tumor is to induce apoptosis of cancer cells and cancer cell death. The curative effects of intraperitoneal chemotherapy was more satisfactory.