摘要
目的研究谷胱甘肽合成抑制剂丁磺氨酸(BSO)对氮芥及环磷酰胺体内外细胞毒作用的影响。方法利用改良MTT法及瘤体称重法检测化疗药对肿瘤细胞生长的抑制作用。结果在体外BSO明显降低人HL_60白血病细胞中谷胱甘肽的含量 ,并显著增强氮芥的细胞毒作用 ,剂量修饰因子为9 19。在体内BSO能增强环磷酰胺对小鼠HepaA肝癌及Lewis肺癌的生长抑制作用 ,抑制率分别由26 1 %升至51 5 %,和由22 6 %升至32 3 %。结论BSO可增强氮芥和环磷酰胺对肿瘤细胞的体内外杀伤作用。
Aim To examine the effects of buthionine sulfoximine (BSO), a specific inhibitor of glutathione (GSH) synthesis,on the cytotoxicity of two alkylating agents, nitrogen mustard (HN2) and cyclophosphamide (CTX) in three cancer cell lines in vitro and in vivo.Methods The cytotoxicity of drugs in vitro and in vivo was assessed by modified MTT assay and tumor_weight reduction, respectively.Results In human leukaemia HL_60 cells, BSO (50 μmol·L-1) pretreatment resulted in marked depletion of cellular GSH (by 87% of control ofter 24 h) and enhanced cytotoxicity of HN2(0.1～0.5 mg·L-1), with dosemodifying factor (DMF) of 9.19 observed. BSO (400,500 mg·kg-1×7,po) and CTX (15,17.5 mg·kg-1×7, ip) combination produced higher responses compared to CTX alone, with the growth inhibition rate increased from 22.6% to 32.3%, and from 26.1% to 51.1% in Lewis_ and Hepa A _ tumor_bearing mice respectively. Conclusion The cytotoxicity of HN2 and CTX can be enhanced by BSO in vitro and in vivo, suggesting the clinical applicability of BSO as a new chemosensitizin agent.
