[Differentiation and apoptosis of NB4 cells synergistically induced by Tanshinone II A and all-trans retinoic acid].

OBJECTIVE: To evalutate the synergistic effects of Tanshinone II A combined with all-trans retinoic acid (ATRA) on the differentiation and apoptosis of human acute promyelocytic leukemia (APL) cell line (NB4).

METHODS: The NB4 cells were treated with 0.5 microg/ml Tanshinone II A combined with 0.5 microg/ml, 0.25 microg/ml and 0.125 microg/ml ATRA respectively in culture. Cells differentiation was demonstrated by morphology and NBT reduction assay. The expression of CD11b and CD33, cell cycle and apoptosis induced by these drugs were measured by flow cytometry (FCM).

RESULTS: The proliferative inhibition rate of the combination of Tan II A with ATRA was much higher. The differentiated cells accounted for over 90 percent, among them the band forms and neutrophils constituted more than 65 percent. NBT reduction and CD11b expression were much higher, and expression of CD33 was lower than that of Tan II A or ATRA alone (P<0.01). FCM analysis also showed that combination of Tan II A with ATRA arrested NB4 cells in G0/G1 phase and induced significantly apoptosis of NB4 cells (P<0.01). There were no significant dose dependent effects induced by ATRA in combination with Tan II A at 0.125 microg/ml to 0.5 microg/ml on differentiation and apoptosis of NB4 cells.

CONCLUSION: The combination of Tan II A with ATRA has synergistic effects on differentiation and apoptosis of NB4 cells. The effects do not increase with the dosage escalation of ATRA.