Objective: To determine the molecular mechanism of reversing multi-drug resistance of K562/AO2 by puerarin.
Methods: Effects of ADR and puerarin on NF-kappaB activity of K562,K562/AO2 were tested by immunofluorescence. The expression of survivin of K562,K562/AO2 was examined by immunocytochemistry. The p-gp expression was detected by flow cytometry.
Results: The NF-kappaB activity of K562 was significantly higher than that of K562/AO2. The NF-kappaB activity of K562 treated by ADR was significantly higher than untreated. The NF-kappaB activity of K562 which was pretreated by puerarin and then treated by ADR was much lower than that treated by ADR alone. The NF-kappaB activity of K562/AO2 intervened by puerarin was lower than that unintervened by puerarin.The p-gp and survivin expression of K562/AO2 was significantly higher than K562. The p-gp and survivin expression of K562 treated by ADR was higher than that untreated by ADR. But the p-gp and survivin expression of K562 which was pretreated by puerarin and then treated by ADR was much lower than that not pretreated by puerarin.The p-gp and survivin expression of K562/AO2 intervened by puerarin was lower than that unintervened by puerarin. The expression was negatively correlated to the duration of intervention. The inhibition effect demonstrated time dependence.
Conclusion: The activation of NF-kappaB can increase the expression of p-gp and survivin, which may be part of the molecular mechanism of multi-drug resistance of K562. Puerarin can prevent and stop the multi-drug resistance in K562 and reverse the multi-drug resistance of K562/AO2 to ADR by inhibiting the activity of NF-kappaB and the expression of p-gp and survivin.
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