谷胱甘肽拮抗环磷酰胺和丙烯醛所致PC_3细胞毒性及小鼠免疫抑制<英文>

Glutathione antagonized cyclophosphamide- and acrolein- induced cytotoxicity of PC_3 cells and immunosuppressive actions in mice

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 study the antagonistic effect of glutathione ( GSH ) on toxicity of PC3 cell induced by cyclophosphamide (Cyc) and acrolein (Acr) and on immunosuppressive actions caused by Cyc. METHODS: Splenocyte, PC3 cell proliferation and cell protein content were measured by tetrazolium (MTT) assay and Coomassie brilliant blue assay. Serum anti-SRBC hemolysin, agglutinin, and splenocyte proliferation were measured in normal and S-180-bearing mice. Tumors were weighed. RESULTS: Pretreatment with GSH 2 mmol·L-1 reduced splenocyte proliferation inhibition from 18.64 %, 49.72 % to 6.78 % , 18.36 % (induced by Cyc 1, and 5 mmol·L-1), and PC3 cell proliferation inhibition from 27.7 % , 45.3 % ,and 74.6 % to 14.6 % , 18.8 % , and 49.1 % (induced by Cyc 1, 3, and 5 mmol·L-1), and from 62.6 %, 85.4 %, and 90.6 % to 41.9 % , 57.7 % , and 86.4 % (induced by Acr 10, 25, and 50 μmol·L-1), respectively. In normal mice, sc GSH 75 or 150 mg·kg-1 bid ×5 d after ip Cyc 40 mg·kg-1, the hemolysin and the splenocyte proliferation were higher than those in normal mice ip Cyc 40 mg·kg-1 alone. Hemolysin, serum agglutinin, and splenocyte proliferation in S-180-bearing mice given sc GSH 150 mg·kg-1 bid×10 d after ip Cyc 40 mg· kg-1 were also markedly higher than those in S-180-bearing mice given ip Cyc alone.But, according to tumor weight, GSH did not interfere the antitumor activity of Cyc in S-180-bearing mice. CONCLUSION: GSH exhibited protective effects against Cyc and Acr, but had no effect on the antitumor action of Cyc.