关键词: 丁磺氨酸, 氮芥, 环磷酰胺, 药物敏感性, 谷胱甘肽

Abstract: 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 - tumoi-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.

Key words: buthionine sulfoximine, nitrogen mustard, cyclophosphamide, glutathione