Antitumor mechanism of danusertib in human AML HL-60 cells |
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| Authors: | HE Si-jia SHU Li-ping REN Tao HE Zhi-xu |
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| Institution: | 1. Department of Pediatrics, The Affiliated Hospital of Guizhou Medical University, Guizhou 550001, China;
2. Cancer Center, Daping Hospital, Third Military Medical University, Chongqing 400042, China |
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| Abstract: | AIM: To investigate the effects of danusertib, a pan-inhibitor of Aurora kinases, on the viability, cell cycle, apoptosis and autophagy of human acute myelocytic leukemia (AML) HL-60 cells.METHODS: The effect of danusertib on the viability of HL-60 cells was examined by MTT assay. The effect of danusertib on apoptosis of HL-60 cells was quantitated by the flow cytometry using an Annexin V/7-AAD apoptosis detection kit. The effect of danusertib on autophagy in the HL-60 cells was assessed by flow cytometry and confocal microscopic analysis. The levels of various proteins related to the cell cycle, apoptosis and autophagy were determined by Western blot.RESULTS: Danusertib decreased the viability of human AML HL-60 cells and induced the cell cycle arrest in G2/M phase. Danusertib also induced mitochon-drium-dependent apoptosis by activation of caspase-3 and autophagy in the HL-60 cells via inhibition of PI3K/Akt/mTOR signaling pathway.CONCLUSION: Danusertib shows effective antitumor ability for promising AML treatment. |
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| Keywords: | PI3K/Akt/mTOR signaling pathway Cell cycle Apoptosis Autophagy HL-60 cells |
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