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目的:观察谷胱甘肽(GSH)在体外对环磷酰胺(Cyc)及其代谢产物丙烯醛(Acr)所致正常小鼠脾细胞增殖抑制和人前列腺癌RC_3细胞体外生长抑制的对抗作用,同时观察GSH在体内对Cyc所致正常小鼠及荷S-180小鼠免疫抑制及抑瘤的影响。方法:用MTT法和考马斯亮蓝法测定正常小鼠脾细胞及人前列腺癌PC_3细胞体外增殖抑制率,并测定小鼠抗SRBC血清溶血素,凝集素含量及脾细胞增殖反应。结果:预先用GSH 2mmol·L~(-1)处理使Cyc 1-5mmol·L~(-1)对小鼠脾细胞的增殖抑制率由18.64%-49.72％降为6.78％-18.36％。对PC_3细胞的生长抑制率由27.7％-74.6％降到14.6％-49.1％。Acr 10-50μmol·L~(-1)对PC_3细胞的生长抑制率为62.6％-90.6％,预先用GSH处理亦可使抑制率降低。GSH对Cyc所致正常小鼠血清溶血素减少与脾细胞增殖抑制有明显的对抗作用,GSH处理并不影响Cyc对荷S-180小鼠的抑瘤作用,但使血清溶血素和凝集素水平及脾细胞增殖能力均显著高于单用Cyc组。结论:GSH减少Cyc,Acr对小鼠脾细胞及PC_3细胞的细胞毒性,GSH与Cyc合用减少Cyc的免疫抑制作用,但不影响Cyc的抗肿瘤作用。
AIM: To observe the antagonistic effect of glutathione (GSH) on the proliferation inhibition of normal mouse spleen cells induced by cyclophosphamide (Cyc) and its metabolite acrolein (Acr) and the growth inhibition of human prostate cancer cell line RC_3 in vitro, At the same time, we observed the effect of GSH on the immunosuppression and anti-tumor of normal mice and S-180 mice induced by Cyc. Methods: The inhibitory rates of proliferation of spleen cells and human prostate cancer PC_3 cells in vitro were determined by MTT assay and Coomassie brilliant blue assay. The levels of anti-SRBC serum hemolysin, lectin and splenocyte proliferation were measured. Results: Pretreatment with GSH 2 mmol·L -1 decreased the inhibitory rate of Cyc 1-5 mmol·L -1 from 18.64% -49.72% to 6.78% -18.36%. The growth inhibition rate on PC 3 cells decreased from 27.7% -74.6% to 14.6% -49.1%. Acr 10-50μmol·L -1 inhibited the growth of PC 3 cells at a rate of 62.6% -90.6%. Pretreatment with GSH also reduced the inhibition rate. GSH had a significant antagonistic effect on the reduction of serum hemolysin and the inhibition of splenocyte proliferation in normal mice. GSH treatment did not affect Cyc inhibition of S-180-loaded mice, but serum hemolysin and lectin levels And spleen cell proliferation were significantly higher than the single Cyc group. CONCLUSION: GSH can reduce the cytotoxicity of Cyc and Acr on mouse splenocytes and PC_3 cells. The combination of GSH and Cyc decreases the immunosuppressive effect of Cyc, but does not affect the anti-tumor effect of Cyc.