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 cytofl uorometry and electrophoresis. Experiments on RLS40 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 specifi c small interfering RNA (siRNA). These fi ndings suggest that active cyclophosphamide metabolite can be a substrate for P-glycoprotein.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 152, No. 9, pp. 318-322, September, 2011
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Patutina, O.A., Mironova, N.L., Logashenko, E.B. et al. Cyclophosphamide metabolite inducing apoptosis in RLS mouse lymphosarcoma cells is a substrate for P-glycoprotein. Bull Exp Biol Med 152, 348–352 (2012). https://doi.org/10.1007/s10517-012-1525-y
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DOI: https://doi.org/10.1007/s10517-012-1525-y