腺病毒介导p21WAF-1联合GM-CSF基因对胃癌荷瘤裸鼠的抑瘤作用的研究

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0．1mL 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。

Antitumor effects of adenovirus-mediated p21WAF-1 combined with GM-CSF genes on transplanted human gastric cancer in nude mice

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.