【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。更多还原

【Abstract】 Objective To investigate the antitumor effects of adenovirus-mediated p21wAF-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-1, GM-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.更多还原