立体定向微量灌注PDGF-B链基因的三链形成寡核苷酸抑制大鼠脑胶质瘤生长  

Inhibition of glioma growth of tumor-bearing rats with triplex forming oligonucleotide of PDGF-B chain microinfused under stereotactic technique

作　　者：李维方[1] 周定标[2] 余新光[2] 金由辛[3] 

机构地区：[1]北京解放军306医院神经外科,100101 [2]解放军总医院神经外科 [3]中国科学院上海生命科学研究院生物化学与细胞生物学研究所分子生物学国家重点实验室

出　　处：《立体定向和功能性神经外科杂志》2004年第5期284-286,共3页Chinese Journal of Stereotactic and Functional Neurosurgery

基　　金："十五"军队科研基金项目 (编号 :0 1MB0 66)

摘　　要：目的　观察在荷瘤大鼠脑内立体定向原位注射血小板源生长因子 (platelet derivedgrowthfactor,PDGF)B链基因的三链形成寡核苷酸 (triplexformingoligonucleotide,TFO)对胶质瘤生长的抑制效果。 方法　在立体定向导引下所有大鼠右尾状核区微量灌注接种 1× 10 6C6胶质瘤细胞 ,其中实验Ⅰ和Ⅱ组在细胞接种后的第 8天 ,开始分别立体定向原位注射TFO 1.5mg/2 0 μl和 3.0mg/2 0 μl的生理盐水 ,以后每隔 72小时原位注射相同剂量的TFO ,共注射 3次。对照组仅在相同时间原位注射 2 0 μl的生理盐水。实验 3周时处死大鼠 ,解剖出全脑 ,观察肿瘤的生长情况 ,测量肿瘤大小 ,标本做常规HE染色和免疫组织化学检查观察肿瘤PDGF B的表达。结果　实验组大鼠有较好的生存状态 ,而对照组在实验 2周时开始出现颅内高压 ,至 3周时大鼠多处于濒危状态。实验Ⅰ组的成瘤抑制率为 6 6 .0 % ,实验Ⅱ组为 92 .2 %。TFO对荷瘤大鼠胶质瘤细胞PDGF B的表达有明显的抑制作用。结论　PDGF B链基因是胶质瘤生长的重要因素 ,应用TFO能取得很好的抗胶质瘤生长的治疗效果。Objective To observe the inhibition effect of triplex forming oligonucleotide(TFO) of PDGF-B chain on glioma tumor growth of tumor-bearing rats.Methods 1×106C 6 glioma cells/20μl liquid with microinfusion were seed into righ caudate putamen of all rats with stereotactic technique.TFO was used in situ with sterotactic technique a week later after glioma cell inoculation.The treated groupⅠandⅡwere treated with TFO of 1.5mg/20μl,3.0mg/20μl liquid 3 times at 8,11,14 days after cell inoculation,respectively.The control group was just treated with 20μl liquid 3 times at the same time.Three weeks after cell inoculation,rats were killed.Samples were detected with HE stain and PDGF-B immunohistochemistry.Results The treated groups had better survival effects.All control rats were in severe danger.The inhibition rate of tumor growth was66.0% in the treated groupⅠ, 92.2% in the treated group Ⅱ.It is obviously significantly different in PDGF-B expression between treated groupⅠ or in the treated group Ⅱand the control group.PDGF-TFO can remarkably inhibites PDGF-B expression of glioma cells of tumor-bearing rats.Conclusion PDGF-B is required for the maintenance and the development of tumor growth of glioma.TFO used in situ could commendably inhibit tumor growth of glioma.

关 键 词：血小板源生长因子 三链形成寡核苷酸 胶质瘤 大鼠 生长 

分 类 号：R739.41[医药卫生—肿瘤]