Mechanism Of Tetrandrine In Combination With Droloxifen To Reverse Multidrug Resistance In Leukemia

Objective: This paper is to study the effect of Tetrandrine in combination with Droloxifen on the expression of NF-кB(nuclear factor kappaB) of K562 and K562/A02 cell lines and to investigate the reversal mechanism of this combination, and to provide theoretic evidence for the clinical application of them as resistance modifying agents.Method: (1) The activation of NF-кB in K562 and K562/A02 cell lines and the effect of Tetrandrine,Droloxifen alone or in combination on NF-кB were determined with Immunocytochemistry and Western blotting respectively. Results: Immunocytochemistry and Western blot analysis demonstrated: (1) K562/A02 cells displayed higher level of NF-кB protein expression than their parental K562 cells;(2) The application of Tetrandrine or Droloxifen alone or in combination had no effect on NF-кB expression in K562 cells at 6h and 12h;(3) Tetrandrine and Droloxifen used alone or in combination could significantly down-regulate NF-кB protein expression in nucleaus of K562/A02 cells. The effect was more significant in combination of Tetrandrine and Droloxifen than the application of single drug.This decrease became more significant at 12h than at 6h.Data was analyzed by SPSS 10.0 software and expressed as mean ± SD.Conclusions: (1) Activation of NF-кB may be involved in the mechanism of MDR of K562/A02 cell line;(2)Inhibition of NF-кB activation may be involved in the mechanism of multidrug resistance reversal to K562/A02 line of Tetrandrine and Droloxifen.