摘要
目的研究脑胶质瘤耐药相关基因蛋白的表达情况,分析其与化疗药物体外敏感性之间的相关性。方法采用组织培养药敏检测法测定50例脑胶质瘤标本对五种不同类型化疗药物:顺铂(cisplatin,DDP)、长春新碱(vincristine,VCR)、替尼泊甙(teniposide,VM26)、尼莫司汀(nimustine,ACNU)和替莫唑胺(temozolomide,TMZ)的体外敏感性(通过计算体外抑制率);同时在组织芯片平台上,运用免疫组织化学法检测耐药相关蛋白O6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)、P-170、TopoⅡ、谷胱苷肽-S-转移酶π(GST-π)的表达,并用免疫组织化学法和原位杂交法检测P53蛋白及p53基因的表达。结果①ACNU体外抑制率与GST-π表达水平之间呈显著性负相关(r=-0.318,P<0.05)。②耐药相关蛋白GST-π与P-170、TopoⅡ表达水平之间呈显著性相关(r分别为0.317和-0.298,P<0.05)。③突变型P53蛋白与野生型p53mRNA之间呈显著性负相关(r=-0.806,P<0.001)。④突变型P53蛋白与TopoⅡ表达水平之间呈显著性相关(r=0.401,P<0.01)。结论肿瘤体外药敏试验结合耐药相关基因蛋白的检测,对于胶质瘤个体化化疗方案的制定及临床化疗疗效的预测等具有重要意义。
Objective To investigate the expression of genes related to drug resistance in glioma, and analyze the relationship between the gene expression and the in vitro chemosensitivity of glioma. Methods The in vitro ctiemosensitivity of 50 brain glioma specimens to five chemotherapeutic agents： cisplatin （DDP）, vincristine （VCR）, teniposide （VM26）, nimustine （ACNU） and temozolomide （TMZ）, was evaluated by tissue culture method, chemosensitivity test and calculating ex vivo inhibition rate. The samples were processed to tissue mieroarray platform. Expressions of multidrug resistance-associated proteins, including O6-methylguanine-DNA methyltransferase （MGMT）, P-170, Topo Ⅱ and glutathione-S-transferasc π （GST-π）, were determined by immtmohistochemical tests. The expressions of P53 protein and p53 mRNA were detected by immunohistochemical tests and in situ hybridization. Results There was a significant negative correlation between in vitro inhibition of ACNU and GST-π expression （r=-0.318, P〈0.05）, and in expression between GST-π and Topo Ⅱ （r=-0.298, P〈0.05） and between mutant P53 protein and wild-type p53 mRNA （r=-0.806, P〈0.001）. A significant positive correlation in expression was observed between GST-π and P-170 （r=0.317, P〈0.05）, and between mutant P53 protein and Topo Ⅱ （r=0.401, P〈0.01）. Conclusion In vitro chemosensitivity test combined with the detection of drug resistance genes and proteins can help formulate the individual chemotherapeutic protocol for glioma and predict the clinical outcomes.
出处
《中国微侵袭神经外科杂志》
CAS
北大核心
2009年第1期33-36,共4页
Chinese Journal of Minimally Invasive Neurosurgery
