9 P - A Possible mechanism of P-glycoprotein regulation in P-388 leukaemia cells

Abstract

The aim of the present study is to try exercising resistant leukaemia cells (LC) regulation by means of glycoconjugates synthesis stimulation using Dolichyl Phosphate (DP) in vitro. P-388 (LC) with induced resistance to Doxorubicin (Dox) (P-388/Dox) were used. DP and P-GP fractions were analysed by HPLC methods. It is confirmed that plasmatic membrans of P-388/Dox LC contain 5,6 – 6,4% of P-GP as a resistance marker. Resistant P-388/Dox LC differ from sensitive ones (P-388/0) in P-GP content by 10–12 times. The study showed 3,5-fold DP decrease in P-388/Dox cells. The investigations demonstrate that the situation can be changed by resistant cells treatment with DP. The DP concentration in P-388/Dox cells was returned to the normal level. It is established that DP in the concentration 10–6 M aid 7–9-fold reducing P-GP in membranes of P-388/Dox cells. The P-388/Dox cells cultivation in medium with DP proceeded to give lowered P-GP content in membranes no over 0,4–0, 6%, which amount was consistent with the level of P-GP in P-388/0 cells. These results indicate that the appearence of multidrug resistance in LC can be regulated using DP. The aim of the present study is to try exercising resistant leukaemia cells (LC) regulation by means of glycoconjugates synthesis stimulation using Dolichyl Phosphate (DP) in vitro. P-388 (LC) with induced resistance to Doxorubicin (Dox) (P-388/Dox) were used. DP and P-GP fractions were analysed by HPLC methods. It is confirmed that plasmatic membrans of P-388/Dox LC contain 5,6 – 6,4% of P-GP as a resistance marker. Resistant P-388/Dox LC differ from sensitive ones (P-388/0) in P-GP content by 10–12 times. The study showed 3,5-fold DP decrease in P-388/Dox cells. The investigations demonstrate that the situation can be changed by resistant cells treatment with DP. The DP concentration in P-388/Dox cells was returned to the normal level. It is established that DP in the concentration 10–6 M aid 7–9-fold reducing P-GP in membranes of P-388/Dox cells. The P-388/Dox cells cultivation in medium with DP proceeded to give lowered P-GP content in membranes no over 0,4–0, 6%, which amount was consistent with the level of P-GP in P-388/0 cells. These results indicate that the appearence of multidrug resistance in LC can be regulated using DP.