Possible role of P-glycoprotein in cyclophosphamide resistance of transplanted mouse RLS lymphosarcoma
Possible role of P-glycoprotein in cyclophosphamide resistance of transplanted mouse RLS lymphosarcoma
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DOI：
10.1007/s10517-005-0358-3
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发表时间：
2005-05-01
影响因子：
0.7
通讯作者：
Lyakhovich, VV
中科院分区：
文献类型：
--
作者：
Grishanova, AY;Mel'nikova, EV;Lyakhovich, VV
本文探讨了小鼠LS淋巴肉瘤及其耐药株RLS对环磷酰胺敏感性不同的原因。LS和RLS细胞分裂在环磷酰胺处理后24 h停止于G（2）/M期，但LS细胞的这种停止持续超过48 h，而RLS细胞的这种停止持续不到24 h。DNA片段，细胞凋亡的标志物，观察到只有在LS细胞从环磷酰胺治疗后24小时开始。LS株和RLS株在bcl-2、bcl-6、bax、bad、mdr 1a、mdr 1b基因和P-糖蛋白的表达上无差异。通过SYTO 16底物从细胞中释放测试，菌株的P-糖蛋白转运活性不同：RLS细胞中的P-糖蛋白活性是LS细胞中的2倍。据推测，RLS肿瘤对环磷酰胺诱导的细胞凋亡的抵抗力是P-糖蛋白抑制细胞凋亡级联反应的结果，P-糖蛋白在这些细胞中的功能比LS细胞中更活跃。
The causes of different sensitivity of mouse LS lymphosarcoma and its resistant RLS variant to cyclophosphamide were studied. Division of LS and RLS cells stops in the G(2)/M phase 24 h after cyclophosphamide treatment, but this stop lasts for more than 48 h in LS cells and less than 24 h in RLS cells. DNA fragmentation, a marker of apoptosis, is observed only in LS cells starting from 24 h after cyclophosphamide treatment. LS and RLS strains do not differ by the expression of bcl-2, bcl-6, bax, bad, mdr1a, mdr1b genes and P-glycoprotein protein. The strains differ by transport activity of P-glycoprotein, tested by SYTO 16 substrate release from cells: activity of P-glycoprotein in RLS cells was 2-fold higher than in LS cells. Presumably, the resistance of RLS tumor to cyclophosphamide-induced apoptosis is a result of inhibition of the apoptotic cascade by P-glycoprotein which is functionally more active in these cells than in LS cells.