O-(氯乙酰-氨甲酰基)烟曲霉醇联合5-氟尿嘧啶对胃癌生长的抑制  

O-chloroacetylcarbamoyl fumagillol combined with 5-fluorouracil in suppression of the growth of gastric cancer

作　　者：宋震亚[1] 彭佳萍[2] 朱永良[1] 钱可大[1] 郑树[2] 

机构地区：[1]浙江大学医学院附属二院,浙江杭州310009 [2]浙江大学肿瘤研究所,浙江杭州310009

出　　处：《中国药理学与毒理学杂志》2003年第1期24-28,共5页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的　以了解和探讨血管生成抑制剂与传统化疗药物联合治疗的可行性及疗效为目的 ,研究血管生成抑制剂O (氯乙酰 氨甲酰基 )烟曲霉醇 (代号TNP 4 70 )联合 5 氟尿嘧啶 (5 FU)对人胃癌裸小鼠皮下瘤的作用。方法　将人胃癌细胞株SGC 790 1sc于32只裸小鼠 ,并随机分成 4组 ,TNP 4 70组 (5 0mg·kg- 1)、5 FU组 (30mg·kg- 1)、联合用药组 (TNP 4 705 0mg·kg- 1+ 5 FU 30mg·kg- 1)及对照组 (含 3%乙醇的 5 %阿拉伯胶 ,每只 0 .2mL) ,均隔日sc。观察皮下瘤长径及短径 ,4周后处死 ,取瘤组织行RT PCR检测VEGF16 5mRNA和免疫组化测定微血管密度 (MVD)。结果　 4周末TNP 4 70组、5 FU组及联合治疗组的抑瘤率分别为 69.7% ,86.7% ,98.8% ,3周末联合治疗组的瘤体积已小于两单一治疗组 (P <0 .0 5 ) ,提示联合治疗对皮下瘤生长的抑制作用明显优于各单一治疗。而各组间VEGF16 5mRNA表达无明显差异 (P >0 .0 5 )。TNP 4 70组、5 FU组、联合治疗组及对照组的MVD计数分别为 3.8± 0 .6,8.8± 4 .8,4 .8± 0 .4 ,8.8± 1.3,TNP 4 70组及联合治疗组的MVD明显较 5 FU治疗组及对照组减少 (P <0 .0 5 ) ;TNP 4 70与联合治疗组之间、5 FU与对照组之间MVD无差异 (P >0 .0 5 )。结论　血管生成抑制剂TNP 4AIM To evaluate the feasibility and anti-tumor effect of combined therapy of O-chloroacetylcarbamoyl fumagillol(TNP-470) and 5-fluorouracil(5-FU) in nu/nu mice model of human gastric cancer. METHODS Thirty two BALB/c nu/nu mice, which had been inoculated human gastric adenocarcinoma cell line subcutaneously, were divided into four groups and received treatment subcutaneously every other day. ① TNP-470 50 mg·kg -1, ② 5-FU 30 mg·kg -1, ③ TNP-470 50 mg·kg -1+5-FU 30 mg·kg -1, ④ TNP-470 vehicle(3% ethanol plus 5% gum arabic in saline). The volume of transplanted tumors were measured every week, after 4 weeks, the nude mice were sacrificed and the tumors were immediately removed for testing the VEGF 165 mRNA by RT-PCR and microvessel density(MVD) by streptavidin-alkaline phosphatase staining method. RESULTS The tumor suppression rates at 4 weeks after inoculation were 98.8%, 69.7% and 86.7%, respectively, in the three treated groups, otherwise the tumor volume in combinated group was more smaller than in other two groups at 3 weeks, combination therapy of TNP-470 with 5-FU showed more marked inhibition on the growth of gastric cancer. But the expression of VEGF 165 mRNA among the four groups had no significant difference (P>0.05). MVD in the four groups were 3.8±0.6, 8.8±4.8, 4.8±0.4, 8.8±1.3, respectively, the MVD in TNP-470 group and combined one were lower than the other two groups (P<0.05), indicating that TNP-470 could inhibit the neovascularization in gastric cancer, whereas 5-FU could not. CONCLUSION Combination therapy of TNP-470 with 5-FU shows more remarkable inhibition on the growth of transplanted gastric cancer in nude mice than single therapy of TNP-470 or 5-FU.

关 键 词：腺癌 胃 血管生成抑制剂 O-(氯乙酰-氨甲酰基)烟曲霉醇 5-氟尿嘧啶 药物治疗 联合 

分 类 号：R735.2[医药卫生—肿瘤]