Brucine对Heps荷瘤小鼠的抗肿瘤作用和毒性的研究

Anti-tumor activity and toxicity of brucine on mice with transplanted Heps

目的观察和评价B ruc ine对移植性肝癌Heps模型荷瘤小鼠的肿瘤抑制作用和生存时间的影响,同时考察B ru-c ine对其免疫系统、造血系统及肝、肾的毒性。方法用ICR♂小鼠接种肝癌Heps瘤株造成移植性肝癌Heps小鼠模型,以B ruc ine对荷瘤小鼠的抑瘤率和生命延长率代表B ruc ine的抗肿瘤活性;以小鼠的体重、免疫器官指数、血细胞指数和肝、肾指数为指标观察B ruc ine对小鼠的毒性及可能的作用机制。结果B ruc ine对移植性肝癌Heps荷瘤小鼠的抑瘤率分别为30.34%(1.61 mg.kg-1)、46.21%(3.23mg.kg-1)和42.07%(6.46 mg.kg-1)。3.23 mg.kg-1(1/20 LD50)是其最佳剂量。但对其生存时间无延长作用。毒性考察实验显示B ruc ine对肝癌Heps小鼠的造血、免疫系统以及肝、肾无明显的毒性。相反B ruc ine还能提高其免疫器官的重量和指数,提高肝癌Heps小鼠的白细胞和血小板数,并能降低小鼠因接种肝癌Heps瘤株而造成的AST、ALT和BUN异常升高。结论B ruc ine能有效抑制移植性肝癌模型荷瘤小鼠体内肿瘤生长,短期对动物的造血、免疫系统以及肝肾没有明显的毒性,相反还能刺激和促进造血系统和免疫系统的功能,恢复小鼠因接种肝癌Heps瘤株而造成的肝肾功能的损伤。通过深入研究B ruc ine有可能发展成为一种新型抗癌药。

Aim To evaluate the effects of Brucine of restraining transplanted tumor growth, prolonging their survival time and its toxicity on haematopoietic and immune systems as well as hepatic and renal function in mice transplanted with Hepatocarcinoma Heps cells. Methods 1CR male mice of Hepatocarcinoma Heps tumor model（ Heps mice）was made through Heps cells inoculation. Anti-tumor activity of Brucine was evaluated in terms of tumor inhibitory ratio and life elongational ratio of mice transplanted with Heps tumor. The toxicity of Brucine was measured the mice weight, immune organ weight, blood cell index（ leukocyte, erythrocyte, platelet, and hemachrome protein）, and hepatic function index （ALT,AST）as well as renal function index（BUN） of Heps mice. Results Brucine had significant restraining effect on the growth of Heps tumor in mice. Its inhibitory rate was 30.34% （ 1.61 mg ·kg^-1）, 46.21%（3.23 mg ·kg^-1）and 42.07% （6. 46 mg ·kg^-1） respectively, and 3.23 mg ·kg^-1 （1/20 LD50） was the best dosage of Brueine for treating Heps tumor in vivo, while Brucine had no distinct effect of prolonging the life of Heps mice. Moreover, it enhanced the weight of body and thymus index as well as spleen index, and had no distinct influence on blood cell index as well as ALT, AST and BUN in Heps mice. Conclusion Brucine can inhibit the growth of transplanted Heps tumor, enhance the weight of immune organ index significantly, and has no toxicity on haematopoietic and immune systems as well as hepatic and renal function of mice transplanted with Heps tumor. It may be developed into a promising anticancer drug through further study