二甲双胍微泡促进表阿霉素抑制移植瘤和及其体内分布研究

Study of transplantation tumor suppression of metformin microbubbles enhanced epirubicin hydrochloride on human lung adenocarcinoma in nude mice

目的研究二甲双胍微泡对人肺腺癌裸鼠移植瘤抑制的影响。方法构建肺腺癌裸鼠皮下移植瘤模型,表阿霉素溶液组和联合二甲双胍微泡化疗药物组,每2 d尾静脉注射5 mg·kg-1药物。正常组和空白脂质微泡组,每2 d尾静脉注射0.9%NaCl和空白脂质微泡(均0.1 mL/20 g)。给药后,测量肿瘤体积变化;在不同时间点(0.5,2,4,8,12,24 h)取大鼠组织。测定载药体系对裸鼠皮下肺腺癌移植瘤的肿瘤抑制率,观察HE染色检测移植瘤及裸鼠各脏器的形态学特征的变化。结果对大鼠肿瘤抑制率,联合二甲双胍微泡化疗药物组与表阿霉素溶液组分别为(86.79±3.13)%,(67.55±3.61)%。表阿霉素在心脏的聚积量,联合二甲双胍微泡疗药物组显著低于表阿霉素溶液组(P<0.05)。结论二甲双胍微泡能促进盐酸表阿霉素抑制人肺腺癌A549细胞体外增殖,具有相对靶向性。

Objective To investigate the inhibitory effect of metformin with lipid microbubbles on human lung adenocarcinoma in nude mice.Methods A model of lung adenocarcinoma xenograft in nude mice was established.Epirubicin group and epirubicin combined with metformin microbubble group （ ECMM） were intravenously injected into drugs at the dose of 5 mg · kg -1 every 2 d.Control group and blank microbubble group were intravenously injected into blank lipid microbubbles at the dose of 0.1 mL/20 g and 0.9%NaCl every 2 d.After treatment , tumor volume was detected.Tissues were obtained at the different time （ 0.5 , 2 , 4 , 8 , 12 , and 24 h ）.The inhibition rate of drug carrier system on lung adenocarcinoma as well as morphological characteristics of HE stai-ning in the nude mice were detected.Results Tumor inhibition rates of epirubicin group and ECMM group were （ 67.55±3.61 ）% and （86.79 ±3.13 ）%, respectively.Accumulation of epirubicin in heart in ECMM group was significantly lower than that in epirubicin group （ P〈0.05 ）.Conclusion Combination with metformin microbubbles en-hances the inhibition of epirubicin on A 549 proliferation in vitro, indica-ting relative targeting.