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裸鼠胰腺癌肝转移模型脂质体阿霉素介入化疗实验观察 被引量:2

Anti-tunor efficacy of interventional chemotherapy with liposomal doxorubicin for hepatic metastasis of pancreatic cancer in nude mouse model
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摘要 目的 观察裸鼠胰腺癌肝转移瘤脂质体阿霉素介入化疗的疗效与毒性反应.方法 建立裸鼠胰腺癌肝转移模型,采用脾脏注射给药模拟介入化疗.按照阿霉素对照组剂量不同分两次实验进行研究,每次实验分6组,每组各7只.实验一分组:脂质体阿霉素高剂量组(6 mg/kg)、中剂量组(3 mg/kg)、低剂量组(1.5 mg/kg),阿霉素组(3 mg/kg),吉西他滨加顺铂组(3 mg/kg)和对照组(100μl 10%葡萄糖);实验二分组:脂质体阿霉素高剂量组(9 mg/kg)、中剂量组(6 mg/kg)、低剂量组(3 mg/kg),阿霉素组(6 mg/kg),吉西他滨加顺铂组(6 mg/kg)和对照组(100μl 10%葡萄糖),观察不同剂量脂质体阿霉素介入化疗对裸鼠胰腺癌肝转移瘤的抑瘤作用.结果 实验一:脂质体阿霉素各剂量组肿瘤平均体积[高剂量(3±1)mm^3,中剂量(55±18)mm^3,低剂量(90±23)mm^3]差异有统计学意义(P<0.05),且疗效呈剂量依赖性,脂质体阿霉素组与相同剂量阿霉素组和吉西他宾加顺铂组相比肿瘤缩小更明显(均P<0.05).各组均未出现明显的毒性反应.实验二:脂质体阿霉素高、中和低剂量组肿瘤体积分别为(11±14)mm^3、(13±4)mm^3、(50±18)mm^3,差异有统计学意义(P<0.05),脂质体阿霉素组与相同剂量阿霉素组相比肿瘤缩小,但差异无统计学意义(P>0.05),与相同剂量吉西他滨加顺铂组相比肿瘤显著缩小(P<0.05).脂质体阿霉素各剂量组均未出现毒性反应,阿霉素组和吉西他滨加顺铂组出现了明显的毒副作用,均有半数动物死亡.结论 脂质体阿霉素用于介入治疗与阿霉素和吉西他滨联合顺铂相比毒性显著降低,疗效显著提高. Objective To investigate the anti-tumor effect of interventional chemotherapy with liposome doxorubicin for hepatic metastasis of pancreatic tumor in nude mice. Methods After the establishment of hepatic metastatic model of pancreatic tumor, the nude mice received various formulations via a spleen injection to imitate the interventional chemotherapy. In each of two following experiments, 42 nude mice were randomly divided into 6 groups. They received liposomal doxorubicin ( including high, intermittent and low-dose), free doxorubicin, gemcitabine plus cisplatin and control respectively. In the first experiment, the doses were 6,3,1.5,3,3 mg/kg and 100 μl 10% glucose for each group respectively. And in the second experiment, 9, 6, 3, 6, 6 mg/kg, and 100 μl 10% glucose respectively. The efficacies of interventional injection of liposomal doxorubicin with different doses were examined in terms of tumor growth retardation for the hepatic metastatic foci of pancreatic tumor. Results In the first experiment, the difference of median hepatic tumor volume was significant among the three groups of mice receiving liposomal doxorubicin with incremental doses in a dose-dependent manner [ high dose: ( 3 ± 1 ) mm^3, middle dose: (55 ± 18) mm^3, low dose: (90 ± 23) mm^3, P 〈 0.05 ]. The liposomal doxorubicin led to a substantial delay of tumor growth as compared to the free drug or gemcitabine plus cisplatin at the same dose ( both P 〈0.05). In addition, all animals were well-tolerated with no obvious acute toxiciry. In the second experiment, significant difference was obtained for the mice injected with different doses of liposomal doxorubicin [ (11 ±4)mm^3, (13±4)mm^3, (50 ± 18)mm^3 ,P〈0.05]. It was correlated with tumor growth delay. The mice administered with either 9 mg/kg or 6 mg/kg were more efficacious to retard tumor growth than those given 3 mg/kg ( P 〈 0. 05 ) . Despite its enhanced effectiveness as compared to mice in gemcitabine plus cisplatin group (P 〈
出处 《中华医学杂志》 CAS CSCD 北大核心 2010年第30期2126-2129,共4页 National Medical Journal of China
基金 国家“863”高技术研究发展计划(2007AA02Z4A6)
关键词 胰腺肿瘤 肿瘤转移 脂质体 治疗结果 介入化疗 Pancreatic neoplasms Neoplasm metastasis Liposomes Treatment outcome Interventional chemotherapy
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