摘要
目的:探讨血管生成抑制剂NM-3联合卡铂对裸鼠皮下种植胃癌细胞生长的影响及可能机制。方法:40只皮下种植人胃腺癌SGC-7901裸小鼠分成生理盐水对照组(2ml/kg)、卡铂治疗组(5mg/kg)、NM-3治疗组(20mg/kg)及联合治疗组(NM-320mg/kg和卡铂5mg/kg),腹腔注射,每周2次。6周后处死动物,取完整肿瘤组织,测量肿瘤体积,计算抑瘤率;常规染色检测胃癌细胞凋亡指数(AI)以及免疫组化染色记数微血管密度(MVD)。结果:(1)生理盐水组、卡铂组、NM-3组及联合组肿瘤体积(mm3)分别为1609.55±41.32、1375.17±38.75、871.26±38.84和548.32±66.02,NM-3组及联合组肿瘤体积均显著小于生理盐水组、卡铂组(P<0.05),且联合组肿瘤体积显著小于NM-3组(P<0.05);卡铂组、NM-3组及联合组抑瘤率分别为14.56%、45.87%、65.93%,联合治疗对裸鼠皮下胃癌生长的抑制作用明显优于各单药治疗。(2)生理盐水组、卡铂组、NM-3组和联合组的MVD计数分别为7.30±0.53、6.98±0.45、4.72±0.51和4.80±0.39,NM-3组及联合组的MVD较卡铂组和生理盐水组明显减少(P<0.05),而卡铂组和生理盐水组之间、NM-3组和联合组之间MVD无差异(P>0.05)。(3)生理盐水组、卡铂组、NM-3组和联合组的胃癌细胞凋亡指数(AI)分别为(2.12±0.29)%、(2.47±0.31)%、(10.43±3.15)%和(12.63±3.75)%,NM-3组及联合组AI均显著高于生理盐水对照组及卡铂组(P<0.05),而生理盐水组和卡铂组、NM-3组以及联合组之间无差异(P>0.05)。结论:血管生成抑制剂NM-3能减少胃癌微血管生成,诱导胃癌细胞凋亡,抑制肿瘤生长,并且能够增强传统细胞毒药物卡铂抗胃癌作用。
Objective：To evaluate the effect of NM-3 combined carboplatin inhibiting the growth of gastric cancer in mice. Methods：Forty BALB/c nu/nu mice, inoculated human gastric cancer cell line SGC-7901 subcutaneously under the dorsal skin, were divided into four groups randomly and received drugs i.p two times a week as following： saline 2ml/kg, carboplatin 5mg/kg, NM-3 20mg/kg, NM-3 20mg/kg and carboplatin 5mg/kg. At the end of sixth week, we sacrificed all mice and removed tumors entirely, then measured the volume of tumors, tested the apoptosis index（AI）of gastric cancer cell by HE staining method and intertumor microvessel density（MVD） by immunohistochemistry staining method.Results：The tumor volume（mm^3） of saline, carboplatin, NM-3 and combinated group were 1 609.55±41.32, 1 575.17±38.75, 871.26±38.84 and 548.32±66.02 respectively, the tumor suppression rates of carboplatin, NM-3 and combined group were 14.56%, 45.87% and 65.93% respectively, and the tumor volume in combined group was smallest than that in other treatment groups（P〈0.05）,indicating that combination therapy of NM-3 combined with carboplatin showed markedly inhibition on the growth of gastric cancer. The MVD in each group were 7.30±0.53, 6.98±0.45, 4.72±0.51 and 4.80±0.39 respectively, the MVD in NM-3 and combined group were lower than the other two groups（P〈0.05）,demonstrating that NM-3 could inhibit the neovascularization in gastric cancer while carboplatin could not. The AI in each group were （2.12±0.29）%, （2.47±0.31）%, （10.43±3.15）% and （12.63±3.75）% respectively and the AI in combined group were lower than carboplatin group （P〈0.05）, Conclusion：The NM-3 can inhibits the growth of tumor by limiting the neovascularization and inducing the apoptosis of gastric cancer. Combinative therapy of NM-3 and carboplat in shows more remarkable inhibition on the growth of transplanted gastric cancer in nude mice than single therapy of NM-3 or carboplatin.
出处
《临床肿瘤学杂志》
CAS
2007年第12期888-892,共5页
Chinese Clinical Oncology
基金
上海市科委自然科学基金项目(02ZB-14072)
关键词
胃癌
血管生成抑制剂
NM-3
卡铂
联合治疗
Gastric cancer
Angiogenesis inhibitors
NM-3
Carboplatin
Combinative therapy.
