Nishikawa M, Nagatomi H, Nishijima M, Ohira G, Chang B J, Sato E, Inoue M
Department of Biochemistry, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka, Japan.
Cancer Lett. 2001 Oct 10;171(2):133-8. doi: 10.1016/s0304-3835(01)00591-2.
Because cis-diamminedichloroplatinum(II) (cisplatin) which generates reactive oxygen species induces renal dysfunction, administration of a large dose for killing cancer cells is highly limited. We recently synthesized a cationic superoxide dismutase (SOD) (hexamethylenediamine-conjugated SOD, AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. Treatment of Ehrlich ascites tumor cells (EATC)-bearing mice with cisplatin sufficient for killing tumor cells increased their motality. The motality of cisplatin-treated EATC-bearing mice was markedly decreased by AH-SOD. These results suggest that targeting SOD to renal proximal tubule cells might permit the administration of high doses of cisplatin and related anticancer agents without causing renal injury.
由于产生活性氧的顺二氯二氨合铂（II）（顺铂）会诱发肾功能障碍，因此为杀死癌细胞而大剂量给药受到很大限制。我们最近合成了一种阳离子超氧化物歧化酶（SOD）（六亚甲基二胺共轭SOD，AH-SOD），它能迅速在肾近端小管细胞中蓄积，并抑制肾脏的氧化损伤。用足以杀死肿瘤细胞的顺铂治疗荷艾氏腹水瘤细胞（EATC）的小鼠，会增加它们的死亡率。AH-SOD可显著降低经顺铂治疗的荷EATC小鼠的死亡率。这些结果表明，将SOD靶向肾近端小管细胞可能允许给予高剂量的顺铂及相关抗癌药物而不引起肾损伤。
