Objective: To evaluate the synergism of Tanshinone II A (Tan II A) and arsenic trioxide (As2O3) on the apoptosis of retinoic acid resistant acute promyelocytic leukemia (APL) cell line (MR2), and to investigate its effect on the expression of P-glycoprotein (Pgp) of MR2 cells.
Methods: As2O3 was added in the media of MR2 cells in a dose of 0.5 micromol/L, 2.0 micromol/L and 5.0 micromol/L, respectively, or combined with Tan II A in a dose of 1.0 microg/ml. The cell proliferation activity was assessed with MTT assay. The cell apoptosis was demonstrated by labeled Annexin V/PI method. The expression of Pgp was evaluated by immunocytochemical assay.
Results: The MR2 cell proliferation activity was obviously inhibited in the two groups of As2O3 0.5 micromol/L, 2.0 micromol/L combined with Tan II A. The inhibitory effect gradually increased with the time extension. In 168 hours, the inhibitory rate of the two combination groups was (90.67+/-5.52)% and (86.70+/- 3.04)%, respectively, significantly stronger than that of corresponding dose of As2O3 alone group (P<0.01). The apoptosis effect of MR2 cell also gradually increased. In 168 hours, the apoptosis rate of the two combination groups was (81.52+/-7.23)% and (90.75+/-6.44)%, respectively, significantly stronger than that of corresponding dose of As2O3 alone group (P<0.01). At the same time, As2O3 alone and combination with Tan II A therapy can significantly reduce the MR2 cell Pgp expression (P<0.01).
Conclusions: There were apoptosis synergism on MR2 cell induced by Tan II A combined with As2O3, at the same time reduced the expression of Pgp in the cells.