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目的 探讨提高BCNU为代表的CENUs对Mer +脑胶质瘤化疗疗效的途径。方法 采用MTT法及测定肿瘤生长观察O6 苄基鸟嘌呤 (O6 BG)预处理Mer+人脑胶质瘤细胞及荷Mer+脑胶质瘤裸小鼠对BCNU疗效的影响。结果 O6 BG能提高BCNU对Mer +胶质瘤细胞T98G的敏感性 2 2倍 ,对Mer 细胞SHG 4 4无增敏作用 ,10 μmol/LO6 BG预处理 2小时即能明显抑制MGMT活性 ,≥5 0 μmol/L时能完全抑制MGMT活性 ;O6 BG毒性极低 ,10 0 μmol/L时细胞生存率 >95 %。O6 BG +BCNU组较空白对照组延缓肿瘤生长 34 16天 ,而单纯BCNU组延缓生长 18天 (P <0 0 1) ,且O6 BG +BCNU组中还见到肿瘤暂时性退缩。结论 O6 BG通过抑制MGMT活性 ,能逆转Mer+人脑胶质瘤细胞对BCNU的耐药性 ,提高BCNU疗效 ,因而可望作为化疗增敏剂与BCNU联合使用
Objective To explore ways to improve the efficacy of CENNU on chemotherapy of Mer + glioma by BCNU. Methods MTT assay and tumor growth were used to observe the effect of O6-benzylguanine (O6 BG) pretreatment on Mer + human glioma cells and nude mice bearing Mer + glioma. Results O6 BG could enhance the sensitivity of BCNU to T98G cells in Mer + glioma cells by 2 to 2 times and no sensitization to SHG 4 cells in Mer cells. The MGMT activity was significantly inhibited by 10 μmol / L LO6 BG pretreatment for 2 hours At 0 μmol / L, MGMT activity was completely inhibited. O6 BG was extremely toxic. The cell viability at 10 μmol / L was> 95%. O6 BG + BCNU group delayed tumor growth for 34-16 days compared with blank control group, while BCNU group only delayed growth for 18 days (P <0.01), and transient tumor regression was found in O6 BG + BCNU group. Conclusion O6 BG can reverse the effect of Mer + human glioma cells on BCNU resistance and increase the efficacy of BCNU by inhibiting the activity of MGMT, which is expected to be used as chemosensitizer in combination with BCNU