腺病毒介导p21^(WAF-1)联合GM-CSF基因对胃癌荷瘤裸鼠的抑瘤作用的研究  

Antitumor effects of adenovirus-mediated p21^(WAF-1)combined with GM-CSF genes on transplanted human gastric cancer in nude mice

作　　者：司若湟[1] 蔡辉[1] 郭杰[1] 李荣范[1] 温世奇[1] 

机构地区：[1]甘肃省人民医院普外科,甘肃兰州730000

出　　处：《兰州大学学报（医学版）》2006年第4期6-8,共3页Journal of Lanzhou University（Medical Sciences）

摘　　要：目的探讨腺病毒介导p21^(WAF-1)：联合GM-CSF基因对胃癌荷瘤裸鼠的抑瘤作用。方法将32只裸鼠建立人胃癌MKN-45细胞移植瘤动物模型。成瘤后动物随机平均分为4组：对照组、p21^(WAF-1)基因治疗组、GM-CSF基因治疗组、p21^(WAF-1)+GM-CSF联合基因治疗组；分别由皮下瘤体内注射重组体腺病毒0．1 mL Ad-LacZ、Ad-p21、Ad-GM、Ad-p21+GM,每周1次,共3次,3个月后观察肿瘤抑制率、肿瘤体积和动物存活情况以及肿瘤组织病理切片。结果(1)联合基因治疗组动物的肿瘤生长受到明显抑制,与单独给予p21^(WAF-1)和GM-CSF基因治疗动物相比,抑制作用显著提高(P＜0．05)；(2)荷瘤小鼠生存期观察,与对照组相比,p21^(WAF-1)基因组和GM-CSF基因组有所延长,联合基因治疗组显著延长(P＜0．01)；(3)病理切片示各基因治疗组肿瘤组织均有出血、坏死和炎性细胞浸润,联合基因治疗组有片状坏死。结论p21^(WAF-1)和GM-CSF两种基因联合治疗胃癌,可以有效抑制肿瘤生长、延长生存期,为胃癌的治疗提供新的思路。Objective To investigate the antitumor effects of adenovirus-mediated p21^WAF-1 combined with GM-CSF genes on transplanted human gastric cancer in nude mice. Methods 32 nude mice were transplanted with human gastric cancer MKN 45 cells to construct tumor models, and divided into 4 groups（8 for each）： control group,p21^WAF-1 gene group, GM-CSF gene group and p21^WAF-1 ＋GM-CSF gene group. Ad-LacZ, Ad-p21, Ad-GM, and Ad-p21＋GM were injected into the tumor respectively. A total of 3 injections, once a week, were given. Observations on tumor suppression rate, tumor volume, the survival time and the histological analysis of the animals were made. Results （1） Tumor growth was obviously suppressed in p21^WAF-1 ＋ GM- CSF gene group when compared with other groups, and the inhibitory effects was much stronger than those of the single gene group; （2） After treatment with a combination of p21^WAF-1 and GM-CSF genes, longer survival time was achieved in mice when compared with controls; （3） The histological analysis showed hemorrhage and necrosis in the tumors treated with p21^WAF-1GM-CSF genes and the combination therapy of p21^WAF-1 and GM-CSF genes. Conclusion Combination administration of p21^WAF-1 and GM-CSF genes can effectively suppress tumor growth, prolong survival time and provide new ideas for the treatment of gastric cancer.

关 键 词：胃肿瘤 p21^WAF-1 GM-CSF 联合基因治疗 

分 类 号：R735.2[医药卫生—肿瘤]