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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 effects of block copolymer electrospun fiber felt (ADR) loaded with adriamycin-degradable L-PLA and polyethylene glycol on implanted hepatocarcinoma in mice. Methods: The mouse model of hepatocellular carcinoma was established by C-57BL mice and H22 hepatocarcinoma cell lines. The mice were divided into experimental group (controlled release group), control group (doxorubicin intratumoral injection group) The control group 2 (doxorubicin intravenous injection group) and the control group 3 (saline intravenous injection group) were measured on the 1st, 3rd, 6th, 9th and 13th day after the administration respectively, and the tumor length The animals were sacrificed on the 14th day, and the tumor samples were stripped to calculate the tumor inhibition rate. At the same time, HE staining was used to detect the expression of apoptosis related protein fas and caspase-3 by flow cytometry Tumor cell apoptosis rate. Results: On the 6th day after administration, the tumor volume increase speed of the experimental group and the control group 1 was less than that of the other groups (P <0.05). On the 9th and 13th day after administration, the tumor volume increase speed of the experimental group was obviously less than Control 1, 2 and 3 groups (P <0.05), on the 14th day experimental group tumor growth inhibition rate was significantly higher than the control group 1 and 2 (P <0.01). The result of immunohistochemistry showed that the apoptosis - related protein fas and the apoptosis related protein caspase - 3 in the experimental group were significantly higher than those in the control group (P <0.01). Flow cytometry showed that the apoptosis rate of tumor cells in the experimental group was significantly higher than that in the control group (P <0.01). CONCLUSION: Adriamycin-loaded delayed release system can inhibit the growth of H22 hepatocellular carcinoma in mice and can significantly accelerate the apoptosis rate of tumor cells.