Role of estrogen receptor/progesterone receptor in toremifene-induced reversal of multidrug resistance in MCF7/ADR cells / 肿瘤

ABSTRACT

Objective: To study the reversing effect of toremifene (TOR) on multidrug resistance (MDR) in drug-resistant (MCF7/ADR) cell lines and its relationship with expression of estrogen receptor/progesterone receptor (ER/PR) in vitro. Methods: SRB method was used to determine the reversal time of toremifene on MDR in MCF7/ADR cells. Flow cytometry was applied to analyze the change in rhodamine 123 fluorescence in MCF7/ADR cells after addition of toremifene. The effect of toremifene on P-glycoprotein (P-gp) expression in MCFT/ADR cells was examined by western blot. Immunohistochemistry was applied to analyze the effect of toremifene on expression of ER/PR. Results: TOR (5, 10, and 20 mol/L) increased the in vitro cytotoxicity of doxorubicin in drug-resistant breast cancer cells (reversing times: 1.5-fold, 7.0-fold and 35.4-fold, respectively) but had no significant effect on drug-sensitive MCF7/S cells. Toremifene significantly enhanced intracellular accumulation of rhodamine 123 in drug-resistant MCF7/ADR cells. The intracellular fluorescence was close to sensitive MCF7/S cells. P-gp had negative expression in MCF7/S cells and was positively expressed in MCF7/ADR cells. TOR (5, 10, and 20 mol/L) had no significantly inhibitory effect on the expression of P-gp in MCF7/ADR cells. The expression of ER was positive and the expression of PR was weak in MCF7/S cells. Both ER and PR were negatively expressed in McF7/ ADR cells. Conclusion: TOR significantly reverses the MDR in MCF7/ADR cells, which is independent of the expression of ER/PR. The possible mechanism may be due to suppression of P-gp expression in MCF7/ADR cells.