沙利度胺对裸鼠原位种植人胃癌生长和转移的抑制作用  

Thalidomide inhibiting growth and metastasis of human gastric cancer implanted in nude mice

作　　者：张国锋[1] 王元和[1] 王强[1] 

机构地区：[1]第二军医大学长征医院普通外科,上海200003

出　　处：《第二军医大学学报》2002年第7期734-737,共4页Academic Journal of Second Military Medical University

摘　　要：目的 :研究沙利度胺对裸鼠原位种植人胃癌生长和转移的抑制作用及其对胃癌细胞凋亡的影响。方法 :建立人胃癌裸鼠原位种植转移模型。随机分为 4组 ,种植 1周后开始 ,分别自腹腔注射生理盐水 (0 .5 ml/ d,对照组 )、5 -氟尿嘧啶 (30 m g·kg- 1 · d- 1 ,5 - FU组 )、沙利度胺 (2 5 0 mg· kg- 1 · d- 1 ,沙利度胺组 )、5 - FU与沙利度胺联合 (5 - FU 30 m g· kg- 1 · d- 1 ,沙利度胺 2 5 0 mg· kg- 1 · d- 1 ,联用组 ) ,1次 / d,共用 5周。种植后第 6周处死动物 ,测量原位肿瘤质量、抑瘤率、肿瘤微血管密度(MVD)、胃癌细胞凋亡指数 (AI) ,观察肿瘤细胞肝、腹膜转移情况。 结果 :5 - FU组、沙利度胺组、联用组的抑瘤率分别为39.8%、4 8.1%、74 .1% ,4组动物肝转移情况分别为 8/ 11、4 / 12、3/ 12、0 / 12 ;腹膜转移分别为 7/ 11、3/ 12、3/ 12、0 / 12。沙利度胺组、联用组 MVD受到明显抑制 (P<0 .0 5 ) ,AI明显增高 (P<0 .0 5 ) ,且以联用组抑制作用最显著 (P<0 .0 5 )。结论 :腹腔注射沙利度胺可通过抑制肿瘤血管生成 ,诱导癌细胞凋亡 ,对胃癌生长和转移具有较强的抑制作用 ,且可与传统腹腔化疗药物联用起协同抑制作用。Objective: To study the inhibition effects of thalidomide on the growth and metastasis of gastric cancer in vivo in nude mice. Methods: Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. Mice were randomly divided into 4 groups: control group (saline solution 0.5 ml, ip), 5 FU group (fluorouracil 30 mg·kg -1 ·d -1 , ip), thalidomide group (thalidomide 250 mg·kg -1 ·d -1 ,ip), combined treatment group (both 5 FU and thalidomide, ip). Six weeks after implantation, the tumor weight, inhibition rates, intratumoral microvessel density (MVD), apoptotic index (AI) and the metastasis were evaluated after the mice were sacrificed. Results: Compared with the control group, growth of tumor was significantly reduced in mice treated with 5 FU, thalidomide and combined treatment (inhibition rate 39.8%, 48.1% and 74.1%). The incidences of liver metastases was also significantly inhibited in the 5 FU group, thalidomide group and combined treatment group than in control group(8/11 vs 4/12, 3/12 and 0/12). The incidences of peritoneal metastases was also significantly inhibited in the 5 FU group, thalidomide group and combined treatment group than in control group(7/11 vs 3/12, 3/12 and 0/12). The MVD decreased significantly in thalidomide group and combined treatment group. AI increased significantly in the treated mice. Conclusion: Thalidomide can induce apoptosis in gastric cancer by inhibiting tumor angiogenesis and has inhibitory effect on growth and metastasis of human gastric cancer implanted in nude mice. Combination of thalidomide with cytotoxic agents is more effective.

关 键 词：胃癌 肿瘤转移 沙利度胺 新生血管化 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤] R730.53[医药卫生—临床医学]