氟尿嘧啶缓释植入剂与注射液腹腔给药治疗H22小鼠腹水瘤对照的研究  

Effects and mechanism of intraperitoneal chemotherapy of sustained-release fluorouracil and ordinary fluorouracil on mice bearing H22 ascitic tumor

作　　者：梅魁敏[1] 秦叔逵[1] 殷晓进[2] 陈亚利[2] 魏红梅 张改琴[4] 

机构地区：[1]解放军八一医院全军肿瘤中心,江苏南京210002 [2]江苏先声药物研究有限公司研究院,江苏南京210042 [3]解放军八八医院肿瘤内科,山东泰安271001 [4]徐州市第三人民医院肿瘤内科,江苏徐州221002

出　　处：《中华肿瘤防治杂志》2012年第15期1144-1148,共5页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的:比较氟尿嘧啶缓释植入剂(中人氟安)和普通氟尿嘧啶注射液(5-FU)两种剂型对H22小鼠腹水瘤模型的抑制作用及其机制。方法:68只H22腹水瘤模型小鼠,随机分为赋形剂对照组、生理盐水对照组、中人氟安组(4mg/只)和5-FU组(4mg/只)。严密观察各组小鼠的一般状态、体质量变化和生存期,计算腹水体积和镜下腹水中每毫升中的肿瘤细胞数,流式细胞仪检测腹水肿瘤细胞凋亡率和S期细胞比例,实时荧光定量RT-PCR(QRT-PCR)和蛋白质印迹法检测腹水肿瘤细胞Bcl-2和bax基因的mRNA和蛋白表达。结果:与两对照组相比,中人氟安组和5-FU组小鼠的一般状态良好,体质量增长缓慢,全身症状出现较晚,生存期延长(14和13dvs 21和19d,P值均<0.01),其中,中人氟安组中位生存期较5-FU组延长,P=0.047。中人氟安组的腹水体积少于5-FU组〔(5.1±0.7)mL vs(7.8±0.9)mL〕,P<0.05;但2组每毫升腹水中的肿瘤细胞数差异无统计学意义〔(7.02±0.98)×108 mL-1 vs(7.86±1.05)×108 mL-1〕;P>0.05。中人氟安组的肿瘤细胞凋亡率和S期比例〔(24.9±5.0)%和(52.19±4.60)%〕均高于5-FU组〔(20.1±4.5)%和(39.25±5.84)%〕,P值均<0.05;同时,前者Bcl-2基因的mRNA与蛋白表达较后者减少(△Ct值为9.57±0.67 vs 7.11±0.35,灰度值为0.22±0.029 vs 0.46±0.480),P值均<0.05;而bax基因的mRNA与蛋白表达较后者增多(△Ct值为2.05±0.21 vs 3.72±0.53,灰度值为0.55±0.026 vs 0.34±0.018),P值均<0.05。结论:同等剂量的中人氟安对于小鼠H22腹水瘤的抑制作用明显强于普通5-FU注射液,其机制可能与前者具有较长的半衰期、明显增加H22腹水瘤细胞凋亡率和S期细胞比例有关。OBJECTIVE： To investigate the inhibited effects and mechanism of intraperitoneal sustained-release flu- orouracil （Sinofuan） chemotherapy compared with ordinary fluorouracil （5-FU） on mice bearing H22 ascitic tumor. METHODS： Six-eight mice models were randomly assigned into 4 groups which were named as control group, saline con trol group, Sinofuan group （4 mg per mice） and 5-FU group （4 mg per mice）. The mice＇s general states, body weight,and survival were observed. The cumulative ascites volume and number of tumor ceils in per millilitre malignant ascites were determined. The apoptosis rates and the cell cycle of H22 ascitic cells were analyzed with flow cytometry and the expres sion of bax and Bcl-2 gene were detected by QRT-PCR and Western Bloting. RESULTS： Compared with the two control group the general state of the Sinofuan and 5-FU group mice were better such as the body weight increased slowly,and thesurvival time were longer （14 and 13 days vs 21 and 19 days, P〈0.01）. Compared with the 5-FU group, the Sinofuan group showed longer survival （P=0. 047） ,lower ascites accumulation （（5.14±0.7） mL vs （7.8±0.9） mL, P〈0.05], similar count of ascites tumor cells [（7. 02±0. 98） ×10^8mL^-1 vs （7.86±1.05） ×10^8mL^-1 ;P〉0. 051 higher apoptosis rates （（24.9±5.0）% vs （20.1±4.5）% P〈0.05],higher S phase percentage （（52.19±4. 60） % vs （39. 25±5.84）%, P〈0. 051 ,lower expression of Bcl-2 gene （△Ct value： 9.57±0.67 vs 7.11±0.35,P〈0.05,Gradation value： 0.22± 0. 029 vs 0. 46±0. 480,P〈0.05） and higher expression of bax gene （ACt value.. 2. 05±0.21 vs 3.72±0.53,P〈0.05; Gradation value： 0.55±0. 026 vs 0. 34 ±0. 018, P〈0.05）. CONCLUSIONS： Sinofuan had a better inhibitive effect on the formation of H22 ascitic tumor in mice than 5-FU. The mechanism may be that Sinofuan has a longer half-life,more apop- tosis and higher S phase percentage on the H22 ascitic tumor cells.

关 键 词：氟尿嘧啶 迟效制剂 输注 胃肠外 腹水 

分 类 号：R730.5[医药卫生—肿瘤]