[Apoptosis of NB4 cells induced by Tanshinone II A combined with arsenic trioxide].
OBJECTIVE
To evaluate the synergistic effects of Tanshinone II A (Tan II A) combined with arsenic trioxide (ATO) on apoptosis and differentiation of NB4 cells.


METHODS
The NB4 cells were treated with Tan II A, ATO, and Tan II A combined with ATO, respectively. The proliferative inhibition rates of NB4 cells induce by Tan II A, ATO and their combination were calculated on the fifth day. The morphology of cell differentiation was observed by Giemsa stain and transmission electron microscope (TEM). The cell cycle, proliferation index and apoptosis induced by these drugs were measured by flow cytometry (FCM).


RESULTS
1) Combination treatment of Tan II A with ATO had synergistic effects on the proliferative inhibition of NB4 cells. This synergistic effects showed a dose and time-dependent manner. The proliferative inhibition rates of NB4 cells were increased gradually after the treatment of 1.0 microg/mL Tan II A combination with 0.125 micromol/L, 0.25 micromol/L and 0.5 micromol/L ATO respectively, which was much higher than those treated by corresponding ATO alone (P < 0.01); 2) Combination treatment of Tan lI A with ATO had synergistic effects on the apoptosis of NB4 cells. The synergistic effects of 1.0 microg/mL Tan II A combined with 0.5 micromol/L ATO on the apoptosis of NB4 cells lasted for 3 days; 3) Combination treatment of Tan II A with ATO had synergistic inhibition effects on proliferation of NB4 cells, which decreased the number of cells in S phase and increased cells in G0/G1 phase. The proliferation indices (PI) of NB4 cells treated with the combination of Tan II A and different level of ATO were lower than those treated by corresponding ATO alone (P < 0.05). Combination treatment of Tan II A with ATO had no significant synergistic effects on the differentiation of NB4 cells.


CONCLUSIONS
Combination treatment of Tan II A with ATO has significant synergistic effects on the apoptosis of NB4 cells. This synergistic effects is related to the dosage and treatment time. The significant synergistic effects of Tan II A and ATO on NB4 cells differentiation is not demonstrated in our experiment.
Zhang
Ge
G
Department of Hematology and Hematologic Research Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China.
Yang
Yi-Ming
YM
Meng
Wen-Tong
WT
Zhou
Jie
J
D045784:Abietanes / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D010087:Oxides / Q000494:pharmacology*
D045784:Abietanes; D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; C021751:tanshinone; D000077237:Arsenic Trioxide