氟尿嘧啶植入剂和注射液在MKN-45裸鼠腹膜移植瘤腹腔化疗中的差异

Inhibitory effect of intraperitoneal chemotherapy with sustained-release fluorouracil vs fluorouracil injection on peritoneally transplanted MKN-45 tumors in nude mice

目的研究氟尿嘧啶植入剂(中人氟安,Sinofuan)和注射液对胃癌细胞腹腔播散化疗疗效的差异及其机制.方法♀BALB/c(nu/nu)裸鼠,每只腹腔注射0.5 m L(含2×106个)MKN-45细胞悬液建立裸鼠腹膜移植瘤模型.选取51只成瘤裸鼠,随机数字法分为对照组、氟尿嘧啶注射液组(2 mg/只)和氟尿嘧啶植入剂组(2 mg/只).严密观察各组裸鼠的一般状态、体质量变化和生存期,测量腹水体积,显微镜下计数每毫升腹水中的肿瘤细胞数,流式细胞仪检测腹水肿瘤细胞凋亡率.结果与对照组相比,氟尿嘧啶注射液组和氟尿嘧啶植入剂组裸鼠的一般状态良好,体质量增长缓慢,全身症状出现较晚,生存期延长(与对照组相比,均P<0.05),其中,氟尿嘧啶植入剂组中位生存期较氟尿嘧啶注射液组亦延长(25 d vs 19 d,P<0.01).氟尿嘧啶植入剂组的腹水体积少于氟尿嘧啶注射液组[(5.66 mL±1.00 mL)vs(8.78 mL±1.19 mL),P<0.01];但两组每毫升腹水中的肿瘤细胞数差异无统计学意义[(2.75×108/m L±0.71×108/m L)vs(3.46×108/mL±0.69×108/mL)].氟尿嘧啶植入剂组的肿瘤细胞凋亡率高于氟尿嘧啶注射液组(14.49%±0.80%vs 2.03%±0.64%,P<0.01).结论氟尿嘧啶植入剂对胃癌腹腔播散有更明显的抑制作用.

AIM To compare the inhibitory effect of sustainedrelease fluorouracil （Sinofuan） and fluorouracil injection on peritoneally transplanted MKN-45 tumors in nude mice. METHODS Fifty-one nude mice peritoneally transplanted with MKN-45 cells were randomly divided into three groups： control group, fluorouracil injection group （2 mg/nude mouse）, and sustained-release fluorouracil group （2 mg/nude mouse）. The general status of the nude mice, body mass changes and survival were observed. Ascites volume was measured, the number of tumor cells per milliliter of ascites was counted, and tumor cell apoptosis was detected.RESULTS Compared with the control group, the general status of nude mice from the fluorouracil injection group and sustained-release fluorouracil group were better with regard to slower weight gain, delt^yed svstemic symptoms and prolonged survival （P 〈 0.05）. The median survival of mice in the sustained- release fluorouracil group was prolonged compared with the fluorouracil injection group （25 d vs 19 d, P 〈 0.01）. Ascites volume in the sustained-release fluorouracil group was less than that in the fluorouracil injection group [（5.66 mL ± 1.00 mL） vs （8.78 mL ± 1.19 mL）, P 〈 0.01], but the difference in the number of ascitic tumor cells per milliliter between the two groups was not statistically significant [（2.75 ×10^8/mL ± 0.71×10^8/mL） vs （3.46 ×10^8/mL ±0.69 ×10^8/mL）]. Tumor cell apoptosis rate was significantly higher in the sustained-release fluorouracil group than in the fluorourewil iniection group （14.49%± 0.80% vs 2.03% ± 0.64%, P 〈 0.01）. CONCLUSION Sustained-release fluorouracil is better than fluorouracil injection in intraperitoneal chemotherapy for peritoneally transplanted MKN-45 tumors in nude mice.