Inhibitory Effect of Small Molecule Compound TIC10 on Leukemia

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.