腹腔内注射羟基喜树碱治疗腹膜转移癌的实验研究

Study on the Intraperitoneal Chemotherapy with Hydroxycamptothecin for the Treatment of Peritoneal Carcinomatosis in Mice

目的:研究腹腔内注射羟基喜树碱(HCPT)对腹膜腔转移癌模型的疗效和安全性。方法:将高转移性人肝癌细胞株HCCLM3接种于30只裸鼠腹腔内,制成腹膜转移癌模型,随机分为治疗组和对照组各15只;前者组按2 mg/kg剂量腹腔内注射HCPT,后者注射等体积的0.85%氯化钠溶液;于第2,4,6周连续注射7 d,观察8周。监测荷瘤裸鼠的体重和腹膜癌的变化,测量血液学和血清学指标。结果:至研究终点时,治疗组14只裸鼠存活,对照组存活5只;治疗组的平均生存期是(55±1)d(95%CI:54-57 d),对照组的平均生存期是(43±4)d(95%CI:34-51 d)(P=0.002)。治疗组的肿瘤重量明显小于对照组。治疗组未观察到血性腹水和腹腔内弥漫性种植灶,对照组有4只裸鼠出现血性腹水,6只出现腹膜腔内弥漫性种植灶(P<0.001)。外周血白细胞计数在治疗组低于对照组(P<0.05),血清甲胎蛋白浓度在治疗组低于对照组(P<0.05),γ-谷氨酰转肽酶活性在治疗组低于对照组(P<0.05)。两组裸鼠的体重、血常规和血生化其他指标均无统计学差异。未观察到明显的药物相关毒副作用。结论:腹腔内注射HCPT治疗腹膜癌模型,能抑制肿瘤生长,减轻腹膜癌病情,延长荷瘤宿主生存期。

Objective： To study the efficacy and safety camptothecin （HCPT） for the treatment of petit of intraperitoneal chemotherapy with hydroxyoneal carcinomatosis in mouse models. Methods. Highly metastatic human HCC cell strain HCCLM3 was injected into the peritoneal cavity of 30 nude mice to construct the model of intraperitoneal carcinomatosis. The mice were randomized in- to treatment group and control group of 15 mice in each group. The former received intraperitomeal injection of HCPT at the dose of 2 mg/kg body weight for 7 days every other week, on the 2nd, 4th and 6th week; and the latter group received the same dose and schedule treatment of 0.85%sodium chloride solution. The mice were observed till natural death or till 56 days. Body weight changes, intraperitoneal carcinomatosis, hematological and biochemical parameters were evaluated. Results： On day 56, 14 mice in the treatment group were still alive, while only 5 in the control group; and the mean survival time was （55±1） days versus （43±4） days （P=0. 002）. The tumor in the control group was significantly smaller than the control group （P=0. 000 28）. No bloody aseites or diffuse peritoneal carcinomatosis were observed in the treatment group, as compared with 4 mice （26.7%） developed bloody ascites and 6 mice （40%） developed diffuse peritoneal carcinomatosis in the control group （P〈0. 001）. The treatment group had significantly lower peripheral blood white blood cell count, lower serum alpha fetoprotein level, and lower serum gamma glutamyl transpeptidase level than the control group （all P〈0.05）. No obvious treatment related toxicities were observed. Conclusion： In this nude mice model of peritoneal carcinomatosis, intraperitoneal injection of HCPT could inhibit tumor progression, reduce the extent of peritoneal carcinomatosis and improve the survival rate of tumor bearing mice.