Effect and Mechanism of Isotetrandrine to Enhance Doxorubicin Sensitivity in Multidrug Resistance Tumor Cells

Objective:To explore the effect and mechanism of Isotetrandrine to enhance doxorubicin (DOX) sensitivity of K562/DOX and MCF-7/DOX cells. Methods: The activity of Isotetrandrine to enhance doxorubicin cytotoxicity was tested using MTT 3-(4, 5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay and evaluated by the reversal fold (RF) values. The level of P-glycoprotein (P-gp) expression and intracellular accumulation of doxorubicin and rhodamine123 (Rh123) were assessed by flow cytometry (FCM). Results The doxorubicin-induced cytotoxicity was significantly potentiated by isotetrandrine with the concentration of 10μg/ml. P-gp was expressed in both K562/DOX cells and MCF-7/DOX cells, but the level of P-gp expression was not distinct difference at the absence or presence of isotetrandrine. The intracellular accumulation of DOX and Rh123 was increased in the presence of isotetrandrine, which indicated that the function of P-gp was effectively inhibited. Conclusion Isotetrandrine exhibited potent effect in the reversal of tumor multidrug resistance (MDR) by inhibiting the function of P-gp in vitro, suggesting that it may become a candidate of effective MDR reversing agents in cancer chemotherapy.