Mitomycin C sensitivity in human bladder cancer cells: possible role of glutathione and glutathione transferase in resistance.
Mitomycin C sensitivity in human bladder cancer cells: possible role of glutathione and glutathione transferase in resistance.
复制标题
人膀胱癌细胞丝裂霉素 C 敏感性：谷胱甘肽和谷胱甘肽转移酶在耐药性中的可能作用。
DOI：
10.1006/abbi.1994.1023
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发表时间：
1994
影响因子：
3.9
通讯作者：
Singh,SV
中科院分区：
文献类型：
--
作者：
Xu,BH;Gupta,V;Singh,SV
在这项研究中，我们研究了敏感性之间的关系，丝裂霉素C（MMC）和谷胱甘肽（GSH）和谷胱甘肽转移酶（GST）水平使用一组三个无关的人膀胱癌细胞系，J82，HT-1197，和SCaBER。细胞系HT-1197和SCaBER对MMC的抗性是J82的2倍和4.5倍。虽然GSH水平在这些细胞系中没有显著差异，但与J82相比，HT-1197和SCaBER细胞中的GST活性分别高出约2.3倍和6.0倍。与GST活性相似，GST π含量在最不敏感细胞系中最高，而在J82细胞中最低。MMC的细胞毒性显着增加，在这些细胞中的预处理与无毒浓度的依他尼酸（EA），GST活性的抑制剂。EA预处理导致这两种细胞中GSH的明显耗竭以及GST活性的抑制。虽然预处理的J82和SCaBER细胞与无毒浓度的D，L-丁硫氨酸-S，R-亚砜亚胺（BSO）引起类似的GSH耗尽，MMC的细胞毒性增强，仅在SCaBER细胞。BSO对MMC细胞毒性在这些细胞系中的差异效应似乎是由于去除BSO后GSH再生程度的差异。而一个显着的GSH再生发生在J82细胞后1小时内BSO去除，这种效果在SCaBER细胞中没有观察到。这些细胞与BSO和EA的联合治疗产生了更大的增强MMC细胞毒性在两个细胞系相比，BSO或EA单独治疗。结论GSH/GST水平可能影响人膀胱癌细胞对MMC的敏感性。
In this study, we have examined the relationship between sensitivity to mitomycin C (MMC) and glutathione (GSH) and glutathione transferase (GST) levels using a panel of three unrelated human bladder cancer cell lines, J82, HT-1197, and SCaBER. Cell lines HT-1197 and SCaBER were about 2- and 4.5-fold more resistant to MMC as compared to J82. Although the GSH level did not differ significantly in these cell lines, GST activity in HT-1197 and SCaBER cells were higher by about 2.3- and 6.0-fold, respectively, as compared to J82. Similar to GST activity, GST π content was highest in the most insensitive cell line and lowest in J82 cells. The cytotoxicity of MMC was increased significantly in these cells by a 1-h pretreatment with a nontoxic concentration of ethacrynic acid (EA), an inhibitor of GST activity. EA pretreatment resulted in a marked GSH depletion as well as GST activity inhibition in both of these cells. Although pretreatment of J82 and SCaBER cells with a nontoxic concentration of D,L-buthionine-S,R-sulfoximine (BSO) caused similar GSH depletion, the cytotoxicity of MMC was enhanced only in SCaBER cells. The differential effect of BSO on MMC cytotoxicity in these cell lines appeared to be due to the differences in the extent of GSH regeneration after removal of BSO. While a marked GSH regeneration occurred in J82 cells within 1 h after BSO removal, such an effect was not observed in SCaBER cells. Combined treatment of these cells with BSO and EA produced a greater potentiation of MMC cytotoxicity in both the cell lines when compared to BSO or EA treatment alone. We conclude that GSH/GST levels may affect the sensitivity of human bladder cancer cells to MMC.