1-甲基色氨酸对荷肝癌小鼠皮下移植瘤生长的抑制作用

Inhibition effect of 1-methyl-tryptophan on transplant hepatocellular carcinoma growth in mice subcutaneous

目的观察1-甲基色氨酸（1-MT）对荷肝癌小鼠皮下移植瘤生长的抑制作用。方法建立荷肝癌小鼠皮下移植瘤模型。实验分为hepG2组、空质粒组、吲哚胺2，3双加氧酶（ID0）生理盐水组、ID05-氟尿嘧啶（5-FU）组、ID01-MT组、ID01-MT和5-FU联合处理组，每组各8只。观测各组小鼠成瘤情况肿瘤体积差异以及常规病理检查变化，并采用免疫组化法检测肿瘤组织内IDO表达情况。结果与hepG2和空质粒生理盐水组比较，IDO生理盐水组肿瘤体积大、生长快（P〈0．05）。与ID0生理盐水组比较，5-FU组、1-MT组和联合处理组肿瘤体积较小、重量减轻，其抑瘤率分别为86．54％、79．95％、94．46％，差异有统计学意义（P〈0．05）。其中联合用药组效果最好（P〈0．05），5-FU组与1-MT组两者间肿瘤体积变化无显著差异（P〉0．05）。HE病理切片观察各处理组可见癌细胞密度减少，坏死区域增加。各处理组外周血甲胎蛋白（AFP）降低，差异有统计学意义（P〈0．05）。结论IDO可促进肝癌细胞的生长，参与了肝癌细胞的免疫逃逸；1-MT对人肝癌小鼠皮下移植瘤生长具有抑制作用，与化疗药联合应用效果更好。

Objective To investigate the inhibitory effect of 1-methyI-tryptophan （1-MT） on transplanted hepatocellular carcinoma in mice. Methods Human hepatocellular carcinoma subcutaneous tumor models were established in mice, and the mice were divided into hepG2 group, empty plasmid group, indoleamine 2,3-dioxygenase （IDO） saline group, IDO 5-fluoropyrimidine （5-FU） group, IDO 1-MT group, and the group combining IDO 1-MT with 5-FU treatment （n= 8 in each group）. The tumor growth, tumor volume and pathological examination were observed and the expression of IDO in tumor tissues was determined by immunohistochemistry. Results Compared with hepG2 and the empty vector saline groups, IDO saline group had bigger tumor, faster growth, and the differences were statistically significant （P〈0.05）. Compared with IDO saline group, 5-FU group, 1-MT group and combination treatment groups showed smaller tumor volume and weight, and the tumor inhibitory rates were 86. 54%, 79. 95%, 94. 46%, respectively. There were significant differences between these groups （P〈0. 05）. However, there were no significant differences in tumor volumes between 5- FU group and 1-MT group （P〉0.05）. HE pathological observation of cells in each treatment group showed reduced density, increased necrotic area and significant decrease in peripheral blood alpha-fetoprotein （P〈0.05）. Conclusions IDO can promote the growth of liver cancer ceils involved in immune escape. 1-MT can inhibit the transplanted tumor growth in mice, and therefore may enhance the che- motherapeutic efficacy.