The aim of the present study was to investigate the synergistic effect of LY294002 (a PI3K inhibitor) and ABT199 (a BCL2 inhibitor) on the cell cycle in acute myeloid leukemia (AML). The optimal concentration and duration of combined LY294002 and ABT199 were determined in human erythroleukemia (K562), promyelocytic leukemia (HL60) and myeloid leukemia (KG1a) cell lines. The mRNA and protein expression levels of cell cycle‑related molecules, including S‑phase kinase‑associated protein 2 (Skp2), p27, BCL2, Bax, cleaved caspase 3 (caspase‑3) and caspase 9 (caspase‑9) were detected via reverse transcription‑quantitative PCR and western blot analysis, respectively. At the molecular level, LY294002 and ABT199 combination treatment significantly downregulated Skp2, Bcl2, procaspase‑3 and procaspase‑9 expression levels, but markedly upregulated p27, Bax, cleaved caspase‑3 and caspase‑9 expression levels in K562, HL‑60 and KG1a cells. The results of the present study demonstrated that LY294002 and ABT199 combination treatment may serve as a novel therapeutic strategy for AML.
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http://dx.doi.org/10.3892/or.2021.8048 | DOI Listing |
Oncol Rep
June 2021
Department of Hematology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
The aim of the present study was to investigate the synergistic effect of LY294002 (a PI3K inhibitor) and ABT199 (a BCL2 inhibitor) on the cell cycle in acute myeloid leukemia (AML). The optimal concentration and duration of combined LY294002 and ABT199 were determined in human erythroleukemia (K562), promyelocytic leukemia (HL60) and myeloid leukemia (KG1a) cell lines. The mRNA and protein expression levels of cell cycle‑related molecules, including S‑phase kinase‑associated protein 2 (Skp2), p27, BCL2, Bax, cleaved caspase 3 (caspase‑3) and caspase 9 (caspase‑9) were detected via reverse transcription‑quantitative PCR and western blot analysis, respectively.
View Article and Find Full Text PDFJ Oncol
August 2019
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Oncogenic KRAS mutation plays a key role in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis with nearly 95% of PDAC harboring mutation-activated KRAS, which has been considered an undruggable target. Doublecortin-like kinase 1 (DCLK1) is often overexpressed in pancreatic cancer, and recent studies indicate that DCLK1+ PDAC cells can initiate pancreatic tumorigenesis. In this study, we investigate whether overexpressing DCLK1 activates RAS and promotes tumorigenesis, metastasis, and drug resistance.
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