摘要
目的:通过对荷瘤小鼠进行异种MMP-2DNA疫苗联合伽玛刀(γ-刀)治疗胶质瘤,了解两者的协同抗瘤作用。方法:制备并纯化异种MMP-2DNA疫苗,建立小鼠胶质瘤荷瘤模型。小鼠荷瘤第二天开始MMP-2DNA疫苗治疗,后肢肌肉注射c-MMP-2DNA疫苗(1mg/ml),100μl/次,每周一次,连续4周。待肿瘤长至约1cm(接种后第16天)开始γ-刀治疗,以50%的等剂量曲线覆盖,边缘剂量13Gy;游标卡尺测量瘤体大小;电子天平称肿瘤重量;绘制胶质瘤模型小鼠的生存曲线;HE染色观察肿瘤组织坏死情况及重要脏器有无病理改变。结果:异种MMP-2DNA疫苗联合伽玛刀治疗胶质瘤荷瘤小鼠的瘤体大小以及荷瘤小鼠的死亡数目小于单独治疗组,生存期明显延长。HE染色显示肿瘤组织坏死明显增多,荷瘤小鼠体内重要脏器无明显病理改变。结论:异种MMP-2DNA疫苗联合伽玛刀治疗胶质瘤能明显抑制肿瘤组织的生长,并延长荷瘤小鼠的生存期,疗效优于单独伽玛刀治疗和MMP-2DNA疫苗治疗,且无明显副作用。证明二者存在协同治疗效应,其联合应用可能是一种独特的抗肿瘤治疗途径。
Objective： To evaluate whether sustained expression of chicken MMP - 2 combine with gamma knife surgery （GKS） can enhance the treatment efficacy of anti - tumor.Methods： A c - MMP - 2 recombinant Plasmids had been constructed and purified for DNA vaccination. Glioma metastatic tumor model were established by injecting i. m into armpit of 5 - to 6 - weeks age of female BALB/C mice.The day after tumor cell inoculation, c - MMP - 2 gene therapy was performed by injecting i.m with 100μl （1mg/ml） DNA once a week for 4 weeks.When tumor glowed into 1 cm, mice were arranged to GKS with prescription curve 50% and prescription dose 13 GY.Tumor size was recorded.After the completion of therapy, measure the dimension of the tumor by vernier caliper and weigh the tumor by electronic balance.Tissue necrosis was observed by HE - staining. Results： As compared with three other control groups, the growth of the tumor tissue and tumor volume of the combined treatment group with GKS and c - MMP - 2 gene therapy significantly reduced and the life span of bearing cancer mice were prolonged as well. In addition, the average tumor weight were lower in GKS combine with c - MMP - 2 group than any others control group. A relatively higher apoptosis cell rate in GKS and c - MMP - 2 group by TUNEL analysis of C6 gliorna tumors. Conclusion： The anti - tumor effect of GKS can be potentiated by e - MMP - 2 gene therapy. These findings suggest a promising way to overcome tumor radiotherapy resistance by c - MMP - 2 gene therapy.
出处
《华西医学》
CAS
2006年第4期758-760,共3页
West China Medical Journal
