三氧化二砷-泊洛沙姆４０７缓释剂瘤内注射治疗裸鼠人肝癌移植瘤的实验研究

目的：观察三氧化二砷-泊洛沙姆４０７（Ａｓ_２Ｏ_３-Ｐ４０７）缓释剂对裸鼠皮下人肝癌移植瘤的有效性。方法：以人肝癌ＨｅｐＧ２细胞为来源建立裸鼠皮下移植瘤模型，实验共分３组：Ａｓ_２Ｏ_３-Ｐ４０７缓释剂治疗组、Ａｓ_２Ｏ_３治疗组和生理盐水（ＮＳ）对照组，于造模成功后６～８天行瘤体注射，每４天１次，共４次。比较各组抗癌疗效，观察裸鼠体重、肿瘤体积变化、抑瘤率、肿瘤组织病理及骨髓涂片以及裸鼠的存活情况、生存质量。结果：Ａｓ２Ｏ３ Ｐ４０７缓释剂治疗组肿瘤生长受到显著抑制，肿瘤体积较Ａｓ_２Ｏ_３组小（Ｐ＜０.０５），瘤重分别为（０.２５７±０.０８０）ｇ和（０.６４１±０.１０９）ｇ，差异有统计学意义（Ｐ＜０.０５）；两组与ＮＳ对照组瘤重（１.０９４±０.１４７）ｇ相比，差异有统计学意义（Ｐ＜０.０５）。治疗后Ａｓ_２Ｏ_３-Ｐ４０７缓释剂组裸鼠体重大于Ａｓ_２Ｏ_３组和ＮＳ对照组，差异有统计学意义（Ｐ＜０.０５）。各组均未见骨髓抑制现象。结论：Ａｓ_２Ｏ_３-Ｐ４０７缓释剂瘤内注射，使用安全，可维持局部有效药物浓度、延长作用时间，疗效优于Ａｓ_２Ｏ_３注射液。

An experimental study of effects of intratumoral injection of arsenic trioxide poloxamer 407 on nude mice transplants of human hepatocellular carcinoma

Objective： To investigate the therapeutic effects of arsenic trioxide poloxamer 407 （As2 O3-P407） depot preparations on the human hepatocellular carcinoma cell line （ HepG2 ） subcutaneously implanted in nude mice. Methods： Nude mice were subcutaneously transplanted with human HepG2 , and then divided into 3 groups. Test group： the nude mice were treated by As2O3-P407; positive control group： the nude mice were treated with As2O3; blank group： the nude mice were treated with physiological saline. 6-8 days after Modeling success, carry out intratumoral injection. Every four days one time, four times totally. To compare the therapeutic effects of three groups, the weight of the nude mice, the changes of tumor size,the inhibitory rate of tumor,the pathology of tumor,the bone marrow smears ,the survival condition of nude mice. Results ：The growth of the tumor of the As2O3-P407 treatment group was significantly inhibited ; the size of the tumor was significant smaller than As2O3 treatment group （ P 〈 0. 05 ） ; the weight of the two groups＇ tumor were significant different （0. 257±0. 080g vs. 0. 641 ±0. 109g, P 〈0. 05）. The weight of the blank group was 1. 094 ±0. 147g and compare with the other two groups, the difference was all significant （P 〈 0. 05 ）. The inhibitory rates of humor about As2O3-P407 and As2O3 treatment groups were 72% and 46%. The weight of the As2O3-P407 treated nude mice was heavier than the other two groups, and the difference was significant （P 〈 0. 05 ）. Bone marrow suppression phenomenon was not observed in three groups. Conclusion：As3O3-P407 through intratumoral injection exhibits therapeutic effects in relatively big advanced liver cancer, because of the high concentration and prolonged action in the tumor foci. Its comprehensive therapeutic effect is better than absolute As2O3administration.