稀土钇-和钐-氟尿嘧啶配合物对荷人胃癌裸鼠皮下移植瘤生长的影响及其毒性

目的研究稀土钇-氟尿嘧啶配合物(Y-FU)和钐-氟尿嘧啶配合物(Sm-FU)对荷人胃癌裸小鼠皮下移植瘤生长的影响及其毒性。方法建立人胃癌裸鼠移植瘤模型,分别ip给予Y-FU和Sm-FU,每周3次,连续4周。通过测定瘤体积和重量观察移植瘤生长,电镜观察和脱氧尿苷三磷酸(dUTP)缺口末端标记技术(TUNEL)检测肿瘤组织中的细胞凋亡。脏器系数和组织病理学检查观察其对主要脏器的影响。结果Y-FU28和56mg·kg-1使瘤重减轻66%和72%,Sm-FU31和62mg·kg-1使瘤重减轻64%和81%,与FU30mg·kg-1组相比瘤重无显著性差异。电镜观察和TUNEL法检测肿瘤组织发现,Y-FU和Sm-FU组移植瘤中有凋亡细胞,TUNEL阳性细胞较5-FU组明显增加。结论Y-FU和Sm-FU对裸鼠人胃癌移植瘤生长有较强的抑制作用,其机制可能与其具有较强的诱导细胞凋亡作用有关。在所观察剂量范围内对主要脏器无明显影响。

Effects and toxicity of yttrium- and samarium-fluorouracil complexes on growth of human gastric carcinoma xenograft tumor in nude mice

AIM To detect anti-tumor activity and toxicity of yttrium- and samarium-fluorouracil complex (Y-FU, Sm-FU) in a human gastric carcinoma cell xenograft model. METHODS A human gastric carcinoma cell (BGC-823) xenograft model in nude mice was prepared. Then these nude mice were treated with Y-FU and Sm-FU (ip) 3 times a week for 4 weeks. The inhibition rate of growth of human gastric carcinoma, the weight indexes and pathological changes in nude mice′s main organs were observed. Induction of apoptosis in the human gastric carcinoma xenograft was observed by electron microscope and TUNEL staining. RESULTS Compared with the normal control group, the growth of human gastric carcinoma was significantly inhibited by Y-FU and Sm-FU without changes in weight and morphology of main organs. The inhibitive rates were 66% and 72% in Y-FU 28 and 56 mg·kg^-1 groups, respectively, and 64% and 81% in Sm-FU 31 and 62 mg·kg^-1 groups, respectively. While, compared with 5-fluorouracil (FU) 30 mg·kg^-1, there was no significant difference in the inhibition rate of growth of gastric carcinoma. TUNEL positive cells were more obviously observed in carcinoma tissues of 2 complexes treated nude mice than FU group. CONCLUSION The growth of human gastric carcinoma is significantly inhibited by Y-FU and Sm-FU, while having no obvious toxicity at certain dose ranges. Their anti-tumor activities are possibly caused by the induction of apoptosis in gastric carcinoma in nude mice.