【摘要】 为逆转胶质瘤的耐药性 ,模拟临床亚硝基脲类药物的用药程序 ,在体外建立由 MGMT介导的人脑胶质瘤耐药细胞系 U2 5 1/ BCNU,并进行细胞耐药性检测和细胞中 MGMTm RNA表达的分析 ;观察 MGMT反义RNA对 U2 5 1/ BCNU细胞 MGMT表达的调节作用及对 U2 5 1/ BCNU细胞 BCNU敏感性的影响。经过 5次用药过程 ,首次在体外成功地建立了对 BCNU具有稳定抗性的 U2 5 1/ BCNU,其对 BCNU的耐受程度约为 U2 5 1的17倍 ;RT- PCR结果显示 ,U 2 5 1/ BCNU细胞有 MGMTm RNA的表达。 MGMT反义 RNA表达载体 p L a MT5 SN和 p L a MTSN能够在一定程度上降低 U2 5 1/ BCNU细胞中 MGMTm RNA的表达水平 ,提高其对 BCNU的敏感性。认为 MGMT反义 RNA能够在一定程度上抑制 MGMT的表达水平 ,提高肿瘤细胞对亚硝基脲类药物的敏感性更多还原

【Abstract】 To reverse the drug resistance of glioma by antisense RNA. Simulating the clinical way of nitrosoureas,a BCNU resistant human glioma subline U251/BCNU was established.The resistance factor and the expression of MGMT mRNA of U251/BCNU were detected.The effect of MGMT antisense RNA on MGMTmRNA expression by RT PCR and the sensitivity to BCNU were observed by RT PCR an MTT assay of U251/BCNU.Result showed that pLaMT5SN and pLaMTSN could down regulated the expression of MGMTmRNA to a certain extent. The sensitivity of aMT5U and aMTU cells to BCNU were 7 and 2 fold higher than that of U251/BCNU cells by MTT assay,This suggest that MGMT antisense RNA could down regulated the expression of MGMT, and enhance the sensitivity of tumor cells to nitrosoureas. Antisense RNA is a effective way to reverse the drug resistance of gliomas, and has prospects for clinical application in the future.更多还原