Effect of curcumin combined with cytarabine on proliferation, autophagy and apoptosis of human acute myeloid leukemia cell line KG1a / 中国药理学通报

ABSTRACT

Aim To investigate the effect of curcumin ( CUR) combined with cytarabine( Ara-C) on the pro-liferation and apoptosis of human acute myeloid leuke-mia cell line KG1a and its relationship with autophagy. Methods The optimal combination concentration of curcumin and cytarabine was screened by MTT method and the combined effects were detected. The effects of CUR and Ara-C on the proliferation, autophagy, apop-tosis and cycle of KG1a cells were analyzed. Results Both CUR and Ara-C significantly inhibited the prolif-eration of KG1a cells ( P<0.05) , and showed a dose-and time-dependent manner. The inhibition rate of cells treated with 40 μmol·L-1CUR and 0.5 μmol· L-1 Ara-C was significantly higher than that of the other doses alone. The survival rate of cells pretreated with 3-MA was significantly decreased ( P <0.05 ) . Auto-phagic vacuoles was observed in cells with Acridine or-ange staining methods, the expression rate of the com-bination group was higher than the single group, and can be inhibited by 3-MA. The apoptosis rate of the combined group was higher than that of the single group. The apoptosis rate of the 3-MA pretreatment group was higher than that of the single group ( P <0.05). Cell numbers of the G0/G1 phase were signifi-cantly more than the S phase. The expression of caspase-3, LC3 and Beclin-1 were up-regulated while the Bcl-2 was down-regulated(P<0.05). The protein level of caspase-3 and Beclin-1 of the combination group was significantly higher than that of the single group ( P <0.05 ) , and the ratio of LC3-Ⅱ/LC3-Ⅰwas increased. The Beclin-1 expression and caspase-3 expression in 3-MA pretreatment group decreased ( P<0.05) . Conclusion Curcumin can induce autoph-agy and apoptosis of KG1a cells and increase the sensi-tivity of leukemic cells to cytarabine. Autophagy inhib-itor 3-MA can not only inhibit the autophagy but also promote apoptosis.