目的:探讨担载阿霉素的可降解左旋聚乳酸和聚乙二醇的嵌段共聚物静电纺丝纤维毡(简称阿霉素缓释系统)对小鼠植入性肝癌的抗肿瘤作用。方法:用C-57BL小鼠和H22肝癌瘤株建立肝癌小鼠模型,并将其分为实验组(缓释剂瘤内植入组)、对照1组(阿霉素瘤内注射组)、对照2组(阿霉素静脉注射组)和对照3组(生理盐水静脉注射组),分别于给药后第1、3、6、9和13天测量肿瘤的长、短径并计算肿瘤体积,第14天处死动物、剥离肿瘤标本,计算抑瘤率;同时对瘤体进行HE染色,行细胞凋亡相关蛋白fas和凋亡相关酶caspase-3的免疫组织化学分析,流式细胞仪检测肿瘤细胞凋亡率。结果:给药后第6天实验组和对照1组小鼠的肿瘤体积增大速度小于其他组(P〈0.05);给药后第9和13天,实验组肿瘤的体积增大速度明显小于对照1、2和3组(P〈0.05),第14天实验组肿瘤生长抑制率明显高于对照1和2组(P〈0.01)。HE染色结果显示实验组瘤体组织坏死程度较重;免疫组化结果显示实验组肿瘤细胞的凋亡相关蛋白fas和凋亡相关酶caspase-3的表达明显高于对照组(P〈0.01);流式细胞仪检测显示实验组肿瘤细胞凋亡率明显高于对照组(P〈0.01)。结论:植入的阿霉素缓释系统对小鼠H22肝癌移植瘤能产生较好的抑制作用,并可明显加快肿瘤细胞的凋亡速度。
Objective To investigate the anti-tumor activity of ADM-fiber on mouse transplanted hepatoma. Methods The ADM-fiber was implanted into H22-bearing C57BL mice. They were divided into four groups: experimental group (ADM-fiber group), control 1 group (ADM intratumorally injection), control 2 group (ADM intravenous injection), control 3 group (physiologic saline intravenous injection). The tumor volume was calculated on the 1st, 3rd, 6th, 9th, 13th day after administration. The tumors were dissected on the 14 th day. This biopsy was weighted and the tumor inhibitory rate was then calculated as formula. Biopsy was then observed with HE staining, analyzed with immunohistochemistry method on the expression of apoptosis relative proteins caspase-3/fas, and the apoptotic rate was analyzed using flow cytometer. Results The growth of tumor volume was slower in experimental group and control 1 group on the 6th day than those in other groups (P〈0.05), it was slower in experimental group than those in the control 1 group on the 9th, 13th day, and it was obviously slower than those in the control 2 and 3 groups on the 9th and 13th day; the inhibitory rate of tumor growth of experinental group was significantly higher than those in the others (P〈0. 01) ; the necrosis of tumor in experimental group was serious than other groups, and the expression of caspase-3/fas was increased numerously in the experimental group (P〈0. 01); compared with control groups, the apoptotic rate was also enhanced substantially in experimental group (P〈0. 01). Conclusion ADM-fiber embedded can exhibit significantly tumor inhibition on mouse H22 transplanted hepatoma, which illustrates that embedding retarders can significantly accelerate the apoptotic rate of tumor cells through ADM-fiber system.