Patutina O A, Mironova N L, Logashenko E B, Popova N A, Nikolin V P, Vasil'ev G V, Kaledin V I, Zenkova M A, Vlasov V V
Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia.
Bull Exp Biol Med. 2012 Jan;152(3):348-52. doi: 10.1007/s10517-012-1525-y.
RLS lymphosarcoma characterized by enhanced expression of mdr1a and mdr1b genes encoding P-glycoprotein is insensitive to low doses of cyclophosphamide, but is susceptible to its high doses approximating the maximum tolerated doses. Induction of apoptotic death of RLS cells by high doses of cyclophosphamide was demonstrated by cytofluorometry and electrophoresis. Experiments on RLS(40) tumor cells derived from RLS lymphosarcoma and characterized by more intensive expression of mdr1a/1b genes showed that the therapeutic effects of cyclophosphamide increased under conditions of simultaneous suppression of these genes by specific small interfering RNA (siRNA). These findings suggest that active cyclophosphamide metabolite can be a substrate for P-glycoprotein.
以编码P-糖蛋白的mdr1a和mdr1b基因表达增强为特征的RLS淋巴瘤对低剂量环磷酰胺不敏感，但对接近最大耐受剂量的高剂量环磷酰胺敏感。通过细胞荧光测定法和电泳证明高剂量环磷酰胺可诱导RLS细胞凋亡死亡。对源自RLS淋巴瘤且以mdr1a/1b基因更强烈表达为特征的RLS(40)肿瘤细胞进行的实验表明，在通过特异性小干扰RNA(siRNA)同时抑制这些基因的条件下，环磷酰胺的治疗效果增强。这些发现表明活性环磷酰胺代谢物可能是P-糖蛋白的底物。
