Abstract
To investigate the inhibitory effect of small molecule compound TIC10 on multiple leukemia cells and its intervention effect on acute myeloid leukemia(AML) induced by MLL-AF9. Leukemia cells (MOLM-13, MV4-11, THP-1, Kasumi-1, KG-1 and K562) were used to detect the inhibitory effect of TIC10 on proliferation of leukemia cells through CCK-8 and cell count. The effect of TIC10 on the cell-cycle of leukemia cells was detected by flow cytometry with BrdU and DAPI staining. Apoptosis was detected by Annexin V and PI staining. Western blot was used to detect the effect of TIC10 on the expression of caspase3, a key apoptosis-associated protein. The intervention effect of TIC10 on the progression of leukemia in vivo was detected by constructing a mouse MLL-AF9 leukemia model. TIC10 treatment significantly inhibited the proliferation of MOLM-13, MV4-11, THP-1, and Kasumi-1 cells(P<0.05). TIC10 treatment substantially reduced the incorporation of BrdU in MV4-11 and Kasumi-1 cells (P<0.01), suggesting that TIC10 inhibited S-phase entry of leukemia cells. Apoptosis assay showed that TIC10 obviously induced apoptosis of leukemia cells(P<0.01). Western blot results showed that TIC10 treatment induced an elevated cleaved-caspase3 protein level in leukemia cells(P<0.05). The results of animal experiments proved that TIC10 effectively interfered with the progression of AML in vivo . TIC10 can effectively inhibite the proliferation of leukemia cells and induce apoptosis, and have a certain intervention effect on AML induced by MLL-AF9, indicating that TIC10 as a potential candidate drug for the treatment of leukemia.
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