三氧化二砷抗裸鼠人结肠癌移植瘤作用及其机制的研究

The Studies on Anti-tumor Effect and Its Mechanism of Arsenic Trioxide for Human Colon Carcinoma in Nude Mouse

目的:探讨三氧化二砷(As2O3)抗人结肠腺癌裸鼠移植瘤作用、作用机制以及药物毒性。方法:建立人结肠癌裸鼠移植瘤模型,随机分为4组,即生理盐水组、5-氟脲嘧啶(5-FU)组、低剂量As2O3组和高剂量As2O3组,比较各组的抑瘤作用和裸鼠一般状态的变化,并对标本分别行光镜和电镜观察、原位末端标记(TUNEL)、免疫组化和血常规检测。结果:As2O3能够明显抑制结肠癌裸鼠移植瘤的增长,并能诱导癌细胞凋亡,调控相关基因表达;未见As2O3引起明显肝、肾和造血系统损害。结论:As2O3对人结肠腺癌细胞裸鼠移植瘤具有显著的抗癌作用,此作用可能与诱导癌细胞凋亡密切相关,且受到多种有关基因的调控;但是对裸鼠的肝、肾和造血系统无明显的毒性。

Objective： To study the effect of arsenic trioxide （As2O3） on human colon carcinoma cell line implanted in nude mice in vivo, as well as the related mechanism and toxicity. Methods： The transplantable human colon carcinoma tumor models in nude mice were established and were divided into 4 groups at random. The anti-tumor effect of every group and general condition of the nude mice were studied. The specimen obtained from the mice were detected by optical microscope, transmission electron microscope （TEM）, TdT-mediated dUTP nick end labeling （TUNEL） and immunohistochemical staining. Also mouse blood routine examinations were made. Results： As2O3 could obviously inhibit the growth of tumor, induce the apoptosis of carcinoma cell and regulate the related genetic expression, and As2O3 didn＇t induce hepatic, renal and hematopoietic system injury in the nude mice. Conclusions： The As2O3 injection has a significant anti-tumor effect on the transplant tumor models for human colon carcinoma in nude mice, which may be related to inducing the apoptosis of carcinoma cell and regulating several genes. As2O3 has no obvious injury for hepatic, renal and hematopoietic system of the nude mice.