Abstract: Objective: To discuss the proliferation inhibition and apoptosis induction of shikonin on the FMS-like tyrosine kinase-3 receptor internal tandem duplication (FLT3-ITD) mutated acute myeloid leukemia (AML) MV4-11 cells, and to preliminarily clarify the molecular mechanisms. Methods: The MV4-11 cells were divided into DMSO group and different concentrations (0.5, 1.0, 2.0, 4.0, and 8.0 μmol·L^-1) of shikonin groups, and treated for 24 and 48 h. The inhibitory rate of proliferation was analyzed by CCK-8 assay, and half inhibitory concentration (IC₅₀) was calculated. The MV4-11 cells were divided into blank control group, DMSO group, and different concentrations (0.25, 0.50, and 1.00 μmol·L^-1) of shikonin groups, and treated for 48 and 72 h; the proliferation rate of cells was analyzed by carbox fluorescenceindiacetate succinimidyl este (CFSE). The MV4-11 cells were divided into DMSO group and different concentrations (0.702, 1.404, and 2.808 μmol·L^-1) of shikonin groups, and treated for 48 h;the apoptotic rate was determined by flow cytometry. The MV4-11 cells were divided into DMSO group and different concentrations (0.351, 0.702, and 1.404 μmol·L^-1) of shikonin groups, and treated for 48 h; the microRNA-155 (miR-155) expression level was detected by Real-time PCR. Results: The results of CCK-8 and CFSE methods indicated that the inhibitory rates of proliferation of MV4-11 cells in different concentrations of shikonin groups were increased compared with DMSO grpup(P<0.05 or P<0.01), and the proliferation rates were decreased (P<0.05 or P<0.01) in a concentration-dependent manner; the IC₅₀ of 24 and 48 h were 1.743 and 1.404 μmol·L^-1, respectively. The flow cytometry results showed that the apoptotic rates of the cells in different concentrations of shikonin groups were increased compared with DMSO group (P<0.01) in a concentration-dependent manner. The Real-time PCR results showed that the expression levels of miR-155 in the cells in different concentrations of shikonin groups were decreased significantly(P<0.01), and the expression level in 1.404 μmol·L^-1 shikonin group was decreased by more than 75%. Conclusion: Shikonin could inhibit the proliferation and promote the apoptosis of FLT3-ITD mutated AML MV4-11 cells, and down-regulate the expression of miR-155, suggesting that shikonin may be one of the potential therapeutic drugs for FLT3-ITD mututed AML.

Key words: acute myeloid leukemia, FMS-like tyrosine kinase-3 receptorinternal tandem duplication, mutation, shikonin, microRNA-155